Transcriptional mechanisms underlying hemoglobin synthesis

Cold Spring Harbor Perspectives in Medicine

Volumn 3, Issue 9, 2013, Pages

  Katsumura, Koichi R ^a   DeVilbiss, Andrew W ^a   Pope, Nathaniel J ^a   Johnson, Kirby D ^a   Bresnick, Emery H ^a  

^a University of Wisconsin Health   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BCL11A PROTEIN, HUMAN; CARRIER PROTEIN; ERYTHROID KRUPPEL-LIKE FACTOR; HEMOGLOBIN; HEMOGLOBIN BETA CHAIN; HEMOGLOBIN F; KRUPPEL LIKE FACTOR; NUCLEAR PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR GATA 1; ZFPM1 PROTEIN, HUMAN;

ANIMAL; BIOSYNTHESIS; CYTOLOGY; ERYTHROID PRECURSOR CELL; GENETICS; HEMOGLOBINOPATHY; HUMAN; KNOCKOUT MOUSE; MOUSE; PHYSIOLOGY; TRANSGENIC MOUSE;

ANIMALS; BETA-GLOBINS; CARRIER PROTEINS; ERYTHROID PRECURSOR CELLS; FETAL HEMOGLOBIN; GATA1 TRANSCRIPTION FACTOR; HEMOGLOBINOPATHIES; HEMOGLOBINS; HUMANS; KRUPPEL-LIKE TRANSCRIPTION FACTORS; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; NUCLEAR PROTEINS; TRANSCRIPTION FACTORS;

EID: 84896144052     PISSN: None     EISSN: 21571422     Source Type: Journal    
DOI: 10.1101/cshperspect.a015412     Document Type: Article

References (227)

1. Anguita E, Hughes J, Heyworth C, Blobel GA, Wood WG, Higgs DR. 2004. Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GAIA-2. EMBOJ 23: 2841-2852.
2. Arceci RJ, King AA, Simon MC, Orkin SH, Wilson DB. 1993. Mouse GATA-4: A retinoic acid-inducible GATA-binding transcription factor expressed in endoder-mally derived tissues and heart. Mol Cell Biol 13: 2235-2246.
3. Atweh GF, Schechter AN. 2001. Pharmacologic induction of fetal hemoglobin: Raising the therapeutic bar in sickle cell disease. Curr Opin Hematol 8: 123-130.
4. Bank A. 2006. Regulation of human fetal hemoglobin: New players, new complexities. Blood 107: 435-443.
5. Bartunek R Kralova J, Blendinger G, Dvorak M, Zenke M. 2003. GATA-1 and c-myb crosstalk during red blood cell differentiation through GATA-1 binding sites in the c-myb promoter. Oncogene 22: 1927-1935.
6. Basu R Morris PE, Haar JL, Wani MA, Lingrel JB, Gaen-sler KM, Lloyd JA. 2005. KLF2 is essential for primitive erythropoiesis and regulates the human and murine embryonic β-like globin genes in vivo. Blood 106: 2566-2571.
7. Bender MA, Bulger M, Close J, Groudine M. 2000a. β-globin gene switching and DNasel sensitivity of the endogenous β-globin locus in mice do not require the locus control region. Mol Cell 5: 387-393.
8. Bender MA, Mehaffey MG, Telling A, Hug B, Ley TJ, Groudine M, Fiering S. 2000b. Independent formation of Dnasel hypersensitive sites in the murine β-globin locus control region. Blood 95: 3600-3604.
9. Bender MA, Roach JN, Halow J, Close J, Alami R, Bou-hassira EE, Groudine M, Fiering SN. 2001. Targeted deletion of 5'HS1 and 5'HS4 of the β-globin locus control region reveals additive activity of the DNasel hypersensitive sites. Blood 98: 2022-2027.
10. BlauCA.StamatoyannopoulosG. 1994. Hemoglobin switching and its clinical implications. Curr Opin Hematol 1: 136-142.
11. Blobel GA, Nakajima T, Eckner R, Montminy M, Orkin SH. 1998. CREB-binding protein cooperates with transcription factor GATA-1 and is required for erythroid differentiation. ProcNatlAcad Sci 95: 2061-2066.
12. Borg J, Papadopoulos P, Georgitsi M, Gutierrez L, Grech G, Fanis P, Phylactides M, Verkerk AJ, van der Spek PJ, Scerri CA, et al. 2010. Haploinsufficiency for the eryth-roid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin. Nat Genet 42: 801-805.
13. Bottardi S, Ross J, Bourgoin V, Fotouhi-Ardakani N, Affar el B, Trudel M, Milot E. 2009. Ikaros and GATA-1 combinatorial effect is required for silencing of human γ-globin genes. Mol Cell Biol 29: 1526-1537.
14. Bresnick EH, Martowicz ML, Pal S, Johnson KD. 2005. Developmental control via GALA factor interplay at chro-matin domains. J Cell Physiol 205: 1-9.
15. Bresnick EH, Johnson KD, Kim SI, Im H. 2006. Establishment and regulation of chromatin domains: Mechanistic insights from studies of hemoglobin synthesis. Prog Nu-deic Acid Res Mol Biol 81: 435-471.
16. Bresnick EH, Lee HY, Fujiwara T, Johnson KD, Keles S. 2010. GALA switches as developmental drivers. J Biol Chem 285:31087-31093.
17. Bresnick EH, Katsumura KR, Lee HY, Johnson KD, Perkins AS. 2012. Master regulatory GALA transcription factors: Mechanistic principles and emerging links to hema-tologic malignancies. Nudeic Acids Res 40: 5819-5831.
18. Bultman SJ, Gebuhr TC, Magnuson T. 2005. A Brgl mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF complexes in β-globin expression and erythroid development. Genes Dev 19: 2849-2861.
19. Bungert J, Dave U, Lim KC, Lieuw KH, Shavit JA, Liu Q, Engel JD. 1995. Synergistic regulation of human β-globin gene switching by locus control region elements HS3 and HS4. Genes Dev 9: 3083-3096.
20. Bungert J, Tanimoto K, Patel S, Liu Q, Fear M, Engel JD. 1999. Hypersensitive site 2 specifies a unique function within the human β-globin locus control region to stimulate globin gene transcription. Mol Cell Biol 19: 3062-3072.
21. Bunn HE 1999. Induction of fetal hemoglobin in sickle cell disease. Blood 93: 1787-1789.
22. Campbell AD, Cui S, Shi L, Urbonya R, Mathias A, Bradley K, Bonsu KO, Douglas RR, Halford B, Schmidt L, et al. 2011. Forced TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes. Proc Natl Acad Sci 108: 18808-18813.
23. Cantor AB, Katz SG, Orkin SH. 2002. Distinct domains of the GALA-1 cofactor FOG-1 differentially influence ery-throid versus megakaryocytic maturation. Mol Cell Biol 22: 4268-4279.
24. Cantor AB, Iwasaki H, Arinobu Y, Moran TB, Shigematsu H, Sullivan MR, Akashi K, Orkin SH. 2008. Antagonism of FOG-1 and GALA factors in fate choice for the mast cell lineage. J Exp Med 205: 611-624.
25. Caterina JJ, Ciavatta DJ, Donze D, Behringer RR, Townes TM. 1994. Multiple elements in human β-globin locus control region 5' HS 2 are involved in enhancer activity and position-independent, transgene expression. Nucleic Acids Res 22: 1006-1011.
26. Cheng Y, Wu W, Kumar SA, Yu D, Deng W, Tripic T, King DC, Chen KB, Zhang Y, Drautz D, et al. 2009. Eryth-roid GALA1 function revealed by genome-wide analysis of transcription factor occupancy, histone modifications, and mRNA expression. Genome Res 19: 2172-2184.
27. Chlon TM, Dore LC, Crispino JD. 2012. Cofactor-mediated restriction of GALA-1 chromatin occupancy coordinates lineage-specific gene expression. Mol Cell 47: 608-621.
28. Collavin L, Gostissa M, Avolio F, Secco P, Ronchi A, San-toro C, Del Sal G. 2004. Modification of the erythroid transcription factor GALA-1 by SUMO-1. Proc Natl Acad Sci 101: 8870-8875.
29. Conaway RC, Sato S, Tomomori-Sato C, Yao T, Conaway JW. 2005. The mammalian mediator complex and its role in transcriptional regulation. Trends Biochem Sci 30: 250-255.
30. Costa FC, Fedosyuk H, Chazelle AM, Neades RY, Peterson KR. 2012. Mi2β is required for γ-globin gene silencing: Temporal assembly of a GATA-1-FOG-1-ML2β repressor complex in β-YAC transgenic mice. PLoS Genet 8: el003155.
31. Crawford SE, Qi C, Misra P, Stellmach V, Rao MS, Engel JD, Zhu Y, Reddy JK 2002. Defects of the heart, eye, and megakaryocytes in peroxisome proliferator activator receptor-binding protein (PBP) null embryos implicate GATA family of transcription factors. J Biol Chem 277: 3585-3592.
32. Crispino JD. 2005. GATA-1 in normal and malignant hema-topoiesis. Semin Cell Dev Biol 16: 137-147.
33. Crispino JD, Lodish MB, MacKay JP, Orkin SH. 1999. Use of altered specificity mutants to probe a specific protein-protein interaction in differentiation: The GATA-l:FOG complex. Mol Cell 3: 219-228.
34. Crossley M, Orkin SH. 1994. Phosphorylation of the erythroid transcription factor GATA-1. J Biol Chem 269: 16589-16596.
35. De Gobbi M, Viprakasit V, Hughes JR, Fisher C, Buckle VJ, Ayyub H, Gibbons RJ, Vernimmen D, Yoshinaga Y, de Jong P, et al. 2006. A regulatory SNP causes a human genetic disease by creating a new transcriptional promoter. Science 312: 1215-1217.
36. De Gobbi M, Anguita E, Hughes J, Sloane-Stanley JA, Sharpe JA, Koch CM, Dunham I, Gibbons RJ, Wood WG, Higgs DR. 2007. Tissue-specific histone modification and transcription factor binding in α globin gene expression. Blood 110: 4503-4510.
37. Dore LC, Chlon TM, Brown CD, White KP, Crispino JD. 2012. Chromatin occupancy analysis reveals genome-wide GATA factor switching during hematopoiesis. Blood 119: 3724-3733.
38. Dorfman DM, Wilson DB, Bruns GA, Orkin SH. 1992. Human transcription factor GATA-2. Evidence for regulation of preproendothelin-1 gene expression in endothe-lial cells. J Biol Chem 267: 1279-1285.
39. Driscoll MC, Dobkin CS, Alter BE 1989. γδβ-Thalassemia due to a de novo mutation deleting the 5' β-globin gene activation-region hypersensitive sites. Proc Natl Acad Sci 86: 7470-7474.
40. Drissen R, Falstra RJ, Gillemans N, Splinter E, Grosveld F, Fhilipsen S, de Laat W. 2004. The active spatial organization of the β-globin locus requires the transcription factor EKLE Genes Dev 18: 2485-2490.
41. Ellis J, Talbot D, Dillon N, Grosveld E 1993. Synthetic human β-globin 5'HS2 constructs function as locus control regions only in multicopy transgene concatamers. EMBO /12: 127-134.
42. Ellis J, Tan-Un KC, Harper A, Michalovich D, Yannoutsos N, Philipsen S, Grosveld E 1996. A dominant chromatin-opening activity in 5' hypersensitive site 3 of the human β-globin locus control region. EMBO J 15: 562-568.
43. Epner E, Reik A, Cimbora D, Telling A, Bender MA, Fie-ring S, Enver T, Martin DI, Kennedy M, Keller G, et al. 1998. The β-globin LCR is not necessary for an open chromatin structure or developmentally regulated transcription of the native mouse β-globin locus. Mol Cell 2: 447-455.
44. Evans T, Felsenfeld G. 1989. The erythroid-specific transcription factor Eryfl: A new finger protein. Cell 58: 877-885.
45. Evans T, Reitman M, Felsenfeld G. 1988. An erythrocyte-specific DNA-binding factor recognizes a regulatory sequence common to all chicken globin genes. Proc Natl Acad Sci 85: 5976-5980.
46. Evans T, Felsenfeld G, Reitman M. 1990. Control of globin gene transcription. Annu Rev Cell Biol 6: 95-124.
47. Fibach E, Burke KP, Schechter AN, Noguchi CT, Rodgers GP. 1993. Hydroxyurea increases fetal hemoglobin in cultured erythroid cells derived from normal individuals and patients with sickle cell anemia or β-thalassemia. Blood 81: 1630-1635.
48. Fiering S, Epner E, Robinson K, Zhuang Y, Telling A, Hu M, Martin DI, Enver T, Ley TJ, Groudine M. 1995. Targeted deletion of 5'HS2 of the murine β-globin LCR reveals that it is not essential for proper regulation of the β-globin locus. Genes Dev 9: 2203-2213.
49. Filipe A, Li Q, Deveaux S, Godin I, Romeo P-H, Stama-topannopoulos G, Mignotte V. 1999. Regulation of embryonic/fetal globin genes by nuclear hormone receptors: A novel perspective on hemoglobin switching. EMBO J 18: 687-697.
50. Forrester WC, Thompson C, Elder JT, Groudine M. 1986. A developmentally stable chromatin structure in the human β-globin locus. Proc Natl Acad Sci 83: 1359-1363.
51. Forrester WC, Takegawa S, Papayannopoulou T, Stamato-yannopoulos G, Groudine M. 1987. Evidence for a locus activation region: The formation of developmentally stable hypersensitive sites in globin-expressing hybrids. Nucleic Acids Res 15: 10159-10177.
52. Forrester WC, Epner E, Driscoll MC, Enver T, Brice M, Papayannopoulou T, Groudine M. 1990. A deletion of the human β-globin locus activation region causes a major alteration in chromatin structure and replication across the entire β-globin locus. Genes Dev 4:1637-1649.
53. Fox AH, Liew C, Holmes M, Kowalski K, MacKay JP, Crossley M. 1999. Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers. EMBO J 18: 2812-2822.
54. Fucharoen S, Siritanaratkul N, Winichagoon P, Chow-thaworn J, Siriboon W, Muangsup W, Chaicharoen S, Poolsup N, Chindavijak B, Pootrakul P, et al. 1996. Hydroxyurea increases hemoglobin F levels and improves the effectiveness of erythropoiesis in β-thalassemia/he-moglobin E disease. Blood 87: 887-892.
55. Fujiwara Y, Browne CP, Cunniff K, Goff SC, Orkin SH. 1996. Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1. Proc Natl Acad Sci 93: 12355-12358.
56. Fujiwara T, O'Geen H, Keles S, Blahnik K, Linnemann AK, Kang YA, Choi K, Farnham PJ, Bresnick EH. 2009. Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy. Mol Cell 36: 667-681.
57. Funnell AP, Norton LJ, Mak KS, Burdach J, Artuz CM, Twine NA, Wilkins MR, Power CA, Hung TT, Per-domo J, et al. 2012. The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo. Mol Cell Biol 32: 3281-3292.
58. Gamsjaeger R, Liew CK, Loughlin FE, Crossley M, Mackay JP. 2007. Sticky fingers: Zinc-fingers as protein-recognition motifs. Trends Biochem Sci 32: 63-70.
59. Gao Z, Huang Z, Olivey HE, Gurbuxani S, Crispino JD, Svensson EC. 2010. FOG-1-mediated recruitment of NuRD is required for cell lineage re-enforcement during haematopoiesis. EMBO J 29: 457-468.
60. Garriga-Canut M, Orkin SH. 2004. Transforming acidic coiled-coil protein 3 (TACC3) controls friend of GATA-1 (FOG-1) subcellular localization and regulates the association between GATA-1 and FOG-1 during hemato-poiesis. JBiol Chem 279: 23597-23605.
61. Goodwin AJ, Mclnerney JM, Glander MA, Pomerantz O, Lowrey CH. 2001. In vivo formation of a human β-globin locus control region core element requires binding sites for multiple factors including GATA-1, NF-E2, erythroid Kriippel-like factor, and Spl. J Biol Chem 276: 26883-26892.
62. Grass JA, Boyer ME, Pal S, Wu J, Weiss MJ, Bresnick EH. 2003. GATA-1-dependent transcriptional repression of GATA-2 via disruption of positive autoregulation and domain-wide chromatin remodeling. Proc Natl Acad Sci 100:8811-8816.
63. Grass JA, Jing H, Kim SI, Martowicz ML, Pal S, Blobel GA, Bresnick EH. 2006. Distinct functions of dispersed GATA factor complexes at an endogenous gene locus. Mol Cell Biol 26: 7056-7067.
64. Gregory GD, Miccio A, Bersenev A, Wang Y, Hong W, Zhang Z, Poncz M, Tong W, Blobel GA. 2010. FOG1 requires NuRD to promote hematopoiesis and maintain lineage fidelity within the megakaryocytic-erythroid compartment. Blood 115: 2156-2166.
65. Grosveld F, van Assendelft GB, Greaves DR, Kollias G. 1987. Position-independent high-level expression of the human β-globin gene in trangsenic mice. Cell 51:975-985.
66. Hardison RC. 2012. Evolution of hemoglobin and its genes. Cold Spring Harb Perspect Med 2: aOl1627.
67. Harju-Baker S, Costa FC, Fedosyuk H, Neades R, Peterson KR. 2008. Silencing of Vglobin gene expression during adult definitive erythropoiesis mediated by GATA-1-FOG-1-ML2 complex binding at the-566 GATA site. Mol Cell Biol 28: 3101-3113.
68. Hatton CS, Wilkie AO, Drysdale HC, Wood WG, Vickers MA, Sharpe J, Ayyub H, Pretorius IM, Buckle VJ, Higgs DR. 1990. α-thalassemia caused by a large (62 kb) deletion upstream of the human α globin gene cluster. Blood 76: 221-227.
69. Higgs DR. 2013. The molecular basis of α-thalassemia. Cold Spring Harb Perspect Med 3:.aOl1718.
70. Hirasawa R, Shimuzu R, Takahashi S, Osawa M, Taka-yanagi S, Kato Y, Onodera M, Minegishi N, Yamamoto M, Fukao K, et al. 2002. Essential and instructive roles of GATA factors in eosinophil development.J Exp Med 195: 1379-1386.
71. Ho IC, Vorhees P, Marin N, Oakley BK, Tsai SF, Orkin SH, Leiden JM. 1991. Human GATA-3: A lineage-restricted transcription factor that regulates the expression of the T cell receptor a gene. EMBO J 10: 1187-1192.
72. Holmes M, Turner J, Fox A, Chisholm O, Crossley M, Chong B. 1999. hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation. J Biol Chem 274: 23491-23498.
73. Hong W, Nakazawa M, Chen YY, Kori R, Vakoc CR, Rakowski C, Blobel GA. 2005. FOG-1 recruits the NuRD repressor complex to mediate transcriptional repression by GATA-1. EMBO J 24: 2367-2378.
74. Horak CE, Mahajan MC, Luscombe NM, Gerstein M, Weissman SM, Snyder M. 2002. GATA-1 binding sites mapped in the β-globin locus using mammalian chip-chip analysis. ProcNatlAcad Sci 99: 2924-2929.
75. Huang Z, Dore LC, Li Z, Orkin SH, Feng G, Lin S, Crispino JD. 2009. GATA-2 reinforces megakaryocyte development in the absence of GATA-1. Mol Cell Biol 29: 5168-5180.
76. Hug BA, Wesselschmidt RL, Fiering S, Bender MA, Epner E, Groudine M, Ley TJ. 1996. Analysis of mice containing a targeted deletion of β-globin locus control region 5' hypersensitive site 3. Mol Cell Biol 16: 2906-2912.
77. Humbles AA, Lloyd CM, McMillan SJ, Friend DS, Xan-thou G, McKenna EE, Ghiran S, Gerard NP, Yu C, Orkin SH, et al. 2004. A critical role for eosinophils in allergic airways remodeling. Science 305: 1776-1779.
78. Hung HL, Lau J, Kim AY, Weiss MJ, Blobel GA. 1999. CREB-binding protein acetylates hematopoietic transcription factor GATA-1 at functionally important sites. Mol Cell Biol 19: 3496-3505.
79. Im H, Grass JA, Johnson KD, Kim SI, Boyer ME, Imbal-zano AN, Bieker JJ, Bresnick EH. 2005. Chromatin domain activation via GATA-1 utilization of a small subset of dispersed GATA motifs within a broad chromosomal region. Proc Natl Acad Sci 102: 17065-17070.
80. Ito E, Toki T, Ishihara H, Ohtani H, Gu L, Yokoyama M, Engel JD, Yamamoto M. 1993. Erythroid transcription factor GATA-1 is abundantly transcribed in mouse testis. Nature 362: 466-468.
81. Jane SM, Nienhuis AW, Cunningham JM. 1995. Hemoglobin switching in man and chicken is mediated by a het-eromeric complex between the ubiquitous transcription factor CP2 and a developmentally specific protein. EMBO J 14: 97-105.
82. Johnson KD, Christensen HM, Zhao B, Bresnick EH. 2001. Distinct mechanisms control RNA polymerase II recruitment to a tissue-specific locus control region and a downstream promoter. Mol Cell 8: 465-471.
83. Johnson KD, Grass JD, Boyer ME, Kiekhaefer CM, Blobel GA, Weiss MJ, Bresnick EH. 2002. Cooperative activities of hematopoietic regulators recruit RNA polymerase II to a tissue-specific chromatin domain. Proc Natl Acad Sci 99: 11760-11765.
84. Johnson KD, Grass JA, Park C, Im H, Choi K, Bresnick EH. 2003. Highly restricted localization of RNApolymerase II within a locus control region of a tissue-specific chromatin domain. Mol Cell Biol 23: 6484-6493.
85. Johnson KD, Kim SI, Bresnick EH. 2006. Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles. Proc Natl Acad Sci 103: 15939-15944.
86. Johnson KD, Boyer ME, Kang JA, Wickrema A, Cantor AB, Bresnick EH. 2007. Friend of GATA-1-independent transcriptional repression: A novel mode of GATA-1 function. Blood 109: 5230-5233.
87. Johnson KD, Hsu AP, Ryu MJ, Wang J, Gao X, Boyer ME, Liu Y, Lee Y, Calvo KR, Keles S, et al. 2012. Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and vascular integrity. J Clin Invest 122: 3692-3704.
88. Kadri Z, Maouche-Chretien L, Rooke HM, Orkin SH, Romeo PH, Mayeux P, Leboulch P, Chretien S. 2005. Phosphatidylinositol 3-kinase/Akt induced by erythro-poietin renders the erythroid differentiation factor GATA-1 competent for TIMP-1 gene transactivation. Mol Cell Biol 25: 7412-7422.
89. Kang YA, Sanalkumar R, O'Geen H, Linnemann AK, Chang CJ, Bouhassira EE, Farnham PJ, Keles S, Bresnick EH. 2012. Autophagy driven by a master regulator of hematopoiesis. Mol Cell Biol 32: 226-239.
90. Katz SG, Cantor AE, Orkin SH. 2002. Interaction between FOG-1 and the corepressor C-terminal binding protein is dispensable for normal erythropoiesis in vivo. Mol Cell Biol 22: 3121-3128.
91. Kelley C, Blumberg H, Zon LI, Evans T. 1993. GATA-4 is a novel transcription factor expressed in endocardium of the developing heart. Development 118: 817-827.
92. Khanna R, Chang SH, Andrabi S, Azam M, Kim A, Rivera A, Brugnara C, Low PS, Liu SC, Chishti AH. 2002. Headpiece domain of dematin is required for the stability of the erythrocyte membrane. Proc Natl Acad Sci 99: 6637-6642.
93. Kiekhaefer CM, Grass JA, Johnson KD, Boyer ME, Bresnick EH. 2002. Hematopoietic-specific activators establish an overlapping pattern of histone acetylation and methylation within a mammalian chromatin domain. Proc Natl Acad Sci 99: 14309-14314.
94. Kim SI, Bresnick EH. 2007. Transcriptional control of erythropoiesis: Emerging mechanisms and principles. Onco-gene 26: 6777-6794.
95. Kim SI, Bultman SJ, Jing H, Blobel GA, Bresnick EH. 2007. Dissecting molecular steps in chromatin domain activation during hematopoietic differentiation. Mol Cell Biol 27:4551-4565.
96. Kim SI, Bresnick EH, Bultman SJ. 2009a. BRGl directly regulates nucleosome structure and chromatin looping of the α globin locus to activate transcription. Nucleic Acids Res 37: 6019-6027.
97. Kim SI, Bultman SJ, Kiefer CM, Dean A, Bresnick EH. 2009b. BRGl requirement for long-range interaction of a locus control region with a downstream promoter. Proc Natl Acad Sci 106: 2259-2264.
98. Ko LJ, Engel JD. 1993. DNA-binding specificities of the GATA transcription factor family. Mol Cell Biol 13: 4011-4022.
99. Kornberg RD. 2005. Mediator and the mechanism oftran-scriptional activation. Trends Biochem Sci 30: 235-239.
100. Kuo CT, Morrisey EE, Anandappa R, Sigrist K, Lu MM, Parmacek MS, Soudais C, Leiden JM. 1997. GÄTA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes Dev 11: 1048-1060.
101. Kutlar A, Ataga K, Reid M, Vichinsky ER Neumayr L, Blair-Britt L, Labotka R, Glass J, Keefer JR, Wargin WA, et al. 2012. A phase 1/2 trial of HQK-1001, an oral fetal globin inducer, in sickle cell disease. Am J Hematol 87: 1017-1021.
102. Lamonica JM, Vakoc CR, Blobel GA. 2006. Acetylation of GATA-1 is required for chromatin occupancy. Blood 108: 3736-3738.
103. Lamonica JM, Deng W, Kadauke S, Campbell AE, Gams-jaeger R, Wang H, Cheng Y, Billin AN, Hardison RC, Mackay JR et al. 2011. Bromodomain protein Brd3 associates with acetylated GATA1 to promote its chromatin occupancy at erythroid target genes. Proc Natl Acad Sci 108:E159-E168.
104. Lavelle D, Saunthararajah Y, Desimone J. 2008. Comment on DNA methylation and mechanism of action of 5-azacy-tidine. Blood 111: 2485.
105. Lee ME, Temizer DH, Clifford JA, Quertermous T. 1991. Cloning of the GALA binding protein that regulates en-dothelin-1 gene expression in endothelial cells. J Biol Chem 266: 16188-16192.
106. Lee HY, Johnson KD, Fujiwara T, Boyer ME, Kim SI, Bresnick EH. 2009. Controlling hematopoiesis through sumoylation-dependent regulation of a GALA factor. Mol Cell 36: 984-995.
107. Lee HY, Johnson KD, Boyer ME, Bresnick EH. 2011. Relo-calizing genetic loci into specific subnuclear neighborhoods. JBiol Chem 286: 18834-18844.
108. Letting DL, Rakowski C, Weiss MJ, Blobel GA. 2003. Formation of a tissue-specific histone acetylation pattern by the hematopoietic transcription factor GATA-1. Mol Cell Biol 23: 1334-1340.
109. Letting DL, Chen YY, Rakowski C, Reedy S, Blobel GA. 2004. Context-dependent regulation of GALA-1 by friend of GATA-1. ProcNatlAcad Sci 101: 476-481.
110. Lettre G. 2012. The search for genetic modifiers of disease severity in the β-hemoglobinopathies. Cold Spring Harb PerspectMed 2: aO15032.
111. Lettre G, Sankaran VG, Bezerra MA, Araujo AS, Uda M, Sanna S, Cao A, Schlessinger D, Costa FF, Hirschhorn JN, et al. 2008. DNA polymorphisms at the BCL11A, HBS1L-MYB, and β-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proc Natl Acad Sci 105: 11869-11874.
112. Liew CK, Simpson RJY, Kwan AHY, Crofts LA, Loughlin FE, Matthews JM, Crossley M, MacKay JP. 2005. Zinc fingers as protein recognition motifs: Structural basis for the GATA-1 /Friend of GATA interaction. Proc Natl Acad Sci 102:583-588.
113. Lim KC, Hosoya T, Brandt W, Ku CJ, Hosoya-Ohmura S, Camper SA, Yamamoto M, Engel JD. 2012. Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning. J Clin Invest 122: 3705-3717.
114. Linnemann AK, O'Geen H, Keles S, Farnham PJ, Bresnick EH. 2011. Genetic framework for GATA factor function in vascular biology. Proc Natl Acad Sci 108: 13641-13646.
115. Liu P, Keller JR, Ortiz M, Tessarollo L, Rachel RA, Nakamura T, Jenkins NA, Copeland NG. 2003. Bcllla is essential for normal lymphoid development. Nat Immunol 4: 525-532.
116. Lopez RA, Schoetz S, DeAngelis K, O'Neill D, Bank A. 2002. Multiple hematopoietic defects and delayed globin switching in Ikaros null mice. Proc Natl Acad Sci 99: 602-607.
117. Lu JR, McKinsey TA, Xu H, Wang DZ, Richardson JA, Olson EN. 1999. FOG-2, a heart-and brain-enriched cofactor for GATA transcription factors. Mol Cell Biol 19: 4495-4502.
118. Lugus JJ, Chung YS, Mills JC, Kim SI, Grass JA, Kyba M, Doherty JM, Bresnick EH, Choi K. 2007. GATA2 functions at multiple steps in hemangioblast development and differentiation. Development 134: 393-405.
119. Mabaera R, Greene MR, Richardson CA, Conine SJ, Kozul CD, Lowrey CH. 2008. Neither DNA hypomethy-lation nor changes in the kinetics of erythroid differentiation explain 5-azacytidine's ability to induce human fetal hemoglobin. Blood 111: 411-420.
120. Macari ER, Lowrey CH. 2011. Induction of human fetal hemoglobin via the NRF2 antioxidant response signaling pathway. Blood 117: 5987-5997.
121. Macari ER, Schaeffer EK, West RJ, Lowrey CH. 2012. Sim-vastatin and t-butylhydroquinone suppress KLF1 and BCL11A gene expression and additively increase fetal hemoglobin in primary human erythroid cells. Blood 121: 830-839.
122. Martin DI, Orkin SH. 1990. Transcriptional activation and DNA binding by the erythroid factor GF-1/NF-El/Eryf 1. Genes Dev 4: 1886-1898.
123. Martowicz ML, Grass JA, Boyer ME, Guend H, Bresnick EH. 2005. Dynamic GATA factor interplay at a multicompo-nent regulatory region of the GATA-2 locus. J Biol Chem 280: 1724-1732.
124. Menzel S, Garner C, Gut I, Matsuda F, Yamaguchi M, Heath S, Foglio M, Zelenika D, Boland A, Rooks H, et al. 2007a. A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2pl5. Nat Genet 39: 1197-1199.
125. Menzel S, Jiang J, Silver N, Gallagher J, Cunningham J, Surdulescu G, Lathrop M, Farrall M, Spector TD, Thein SL. 2007b. The HBS1L-MYB intergenic region on chromosome 6q23.3 influences erythrocyte, platelet, and monocyte counts in humans. Blood 110:3624-3626.
126. Merika M, Orkin SH. 1993. DNA-binding specificity of GATA family transcription factors. Mol Cell Biol 13: 3999-4010.
127. Miccio A, Blobel GA. 2010. Role of the GATA-l/FOG-1/ NuRD pathway in the expression of human β-like globin genes. Mol Cell Biol 30: 3460-3470.
128. Miccio A, Wang Y, Hong W, Gregory GD, Wang H, Yu X, Choi JK, Shelat S, Tong W, Poncz M, et al. 2010. NuRD mediates activating and repressive functions of GATA-1 and FOG-1 during blood development. EMBO J 29: 442-456.
129. Migliaccio AR, Rana RA, Sanchez M, Lorenzini R, Centurione L, Bianchi L, Vannucchi AM, Migliaccio G, Orkin SH. 2003. GATA-1 as a regulator of mast cell differentiation revealed by the phenotype of the GATA-1 °™ mouse mutant. J Exp Med 197: 281-296.
130. Miller IJ, Bieker JJ. 1993. A novel, erythroid cell-specific murine transcription factor that binds to the CACCC element and is related to the Krtippel family of nuclear proteins. Mol Cell Biol 13: 2776-2786.
131. Mohseni M, Chishti AH. 2008. The headpiece domain of dematin regulates cell shape, motility, and wound healing by modulating RhoA activation. Mol Cell Biol 28: 4712-4718.
132. Molkentin JD, Lin Q, Duncan SA, Olson EN. 1997. Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev 11: 1061-1072.
133. Morrisey EE, Ip HS, Lu MM, Parmacek MS. 1996. GATA-6: A zinc finger transcription factor that is expressed in multiple cell lineages derived from lateral mesoderm. Dev Biol 177: 309-322.
134. Morrisey EE, Ip HS, Tang Z, Lu MM, Parmacek MS. 1997. GATA-5: A transcriptional activator expressed in a novel temporally and spatially-restricted pattern during embryonic development. Dev Biol 183: 21-36.
135. Navas PA, Peterson KR, Li Q, Skarpidi E, Rohde A, Shaw SE, Clegg CH, Asano H, Stamatoyannopoulos G. 1998. Developmental specificity of the interaction between the locus control region and embryonic or fetal globin genes in transgenic mice with an HS3 core deletion. Mol Cell Biol 18: 4188-4196.
136. Navas PA, Peterson KR, Li Q, McArthur M, Stamatoyannopoulos G. 2001. The 5'HS4 core element of the human β-globin locus control region is required for high-level globin gene expression in definitive but not in primitive erythropoiesis. J Mol Biol 312: 17-26.
137. Nichols KE, Crispino JD, Poncz M, White JG, Orkin SH, Maris JM, Weiss MJ. 2000. Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. Nat Genet 24: 266-270.
138. Nienhuis AW, Nathan DG. 2012. Pathophysiology and clinical manifestations of the β-thalassemias. Cold Spring Harb Perspect Med 2: aOl1726.
139. Orkin SH. 1990. Globin gene regulation and switching: Circa 1990. Cell 63: 665-672.
140. Orkin SH, Higgs DR. 2010. Medicine. Sickle cell disease at 100 years. Science 329: 291-292.
141. Pace BS, Qian XH, Sangerman J, Ofori-Acquah SF, Ba-liga BS, Han J, Critz SD. 2003. p38 MAP kinase activation mediates γ-globin gene induction in erythroid progenitors. Exp Hematol 31: 1089-1096.
142. Pal S, Cantor AB, Johnson KD, Moran TB, Boyer ME, Orkin SH, Bresnick EH. 2004. Coregulator-dependent facilitation of chromatin occupancy by GATA-1. Proc NatlAcad Sci 101: 980-985.
143. Pawlik KM, Townes TM. 1995. Autonomous, erythroid-spe-cific DNase I hypersensitive site formed by human β-globin locus control region (LCR) 5' HS 2 in transgenic mice. Dev Biol 169: 728-732.
144. Perkins AC, Sharpe AH, Orkin SH. 1995. Lethal β-thalas-saemia in mice lacking the erythroid CACCC-transcrip-tion factor EKLE Nature 375: 318-322.
145. Persons DA, Allay JA, Allay ER, Ashmun RA, Orlic D, Jane SM, Cunningham JM, Nienhuis AW. 1999. Enforced expression of the GATA-2 transcription factor blocks normal hematopoiesis. Blood 93: 488-499.
146. Peterson KR, Clegg CH, Navas PA, Norton EJ, Kim-brough TG, Stamatoyannopoulos G. 1996. Effect of deletion of 5'HS3 or 5'HS2 of the human β-globin locus control region on the developmental regulation of globin gene expression in β-globin locus yeast artificial chromosome transgenic mice. Proc NatlAcad Sci 93:6605-6609.
147. Pevny L, Simon MC, Robertson E, Klein WH, Tsai SF, D'Agati V, Orkin SH, Costantini E 1991. Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature 349: 257-260.
148. Pevny L, Lin CS, D'Agati V, Simon MC, Orkin SH, Costantini E 1995. Development of hematopoietic cells lacking transcription factor GATA-1. Development 121: 163-172.
149. Philipsen S, Talbot D, Fraser P, Grosveld E 1990. The β-globin dominant control region: Hypersensitive site 2. EMBO 79:2159-2167.
150. Philipsen S, Pruzina S, Grosveld E 1993. The minimal requirements for activity in transgenic mice of hypersensitive site 3 of the β globin locus control region. Embo J 12: 1077-1085.
151. Pomerantz O, Goodwin AJ, Joyce T, Lowrey CH. 1998. Conserved elements containing NF-E2 and tandem GATA binding sites are required for erythroid-specific chroma-tin structure reorganization within the human β-globin locus control region. Nucleic Acids Res 26: 5684-5691.
152. Pope NJ, Bresnick EH. 2010. Differential coregulator requirements for function of the hematopoietic transcription factor GATA-1 at endogenous loci. Nucleic Acids Res 38: 2190-2200.
153. Pruzina S, Hanscombe O, Whyatt D, Grosveld F, Philipsen S. 1991. Hypersensitive site 4 of the human β globin locus control region. Nucleic Acids Res 19: 1413-1419.
154. Pruzina S, Antoniou M, Hurst J, Grosveld F, Philipsen S. 1994. Transcriptional activation by hypersensitive site three of the human β-globin locus control region in murine erythroleukemia cells. Biochim Biophys Ada 1219: 351-360.
155. Raich N, Clegg CH, Grofti J, Romeo PH, Stamatoyannopoulos G. 1995. GATA1 and YY1 are developmental repressors of the human ε-globin gene. EMBO J 14: 801-809.
156. Rana AP, Ruff P, Maalouf GJ, Speicher DW, Chishti AH. 1993. Cloning of human erythroid dematin reveals another member of the villin family. Proc Natl Acad Sci 90: 6651-6655.
157. Reik A, Telling A, Zitnik G, Cimbora D, Epner E, Grou-dine M. 1998. The locus control region is necessary for gene expression in the human β-globin locus but not the maintenance of an open chromatin structure in erythroid cells. Mol Cell Biol 18: 5992-6000.
158. Rodgers GP, Dover GJ, Noguchi CT, Schechter AN, Nienhuis AW. 1989. Induction of fetal hemoglobin in sickle cell patients by hydroxyurea: The N.I.H. experience. Prog Clin Biol Res 316B: 281-293.
159. Rodgers GP, Dover GJ, Uyesaka N, Noguchi CT, Schechter AN, Nienhuis AW. 1993. Augmentation by erythropoietin of the fetal-hemoglobin response to hydroxyurea in sickle cell disease. NEnglJMed 328: 73-80.
160. Ross J, Mavoungou L, Bresnick EH, Milot E. 2012. GATA-1 utilizes Ikaros and polycomb repressive complex 2 to suppress Hesl and to promote erythropoiesis. Mol Cell Biol 32: 3624-3638.
161. Rupon JW, Wang SZ, Gaensler K, Lloyd J, Cinder CD. 2006. Methyl binding domain protein 2 mediates γ-globin gene silencing in adult human βYAC transgenic mice. Proc Natl Acad Sci 103: 6617-6622.
162. Rupon JW, Wang SZ, Gnanapragasam M, Labropoulos S, Cinder GD. 2011. MBD2 contributes to developmental silencing of the human ε-globin gene. Blood Cells Mol Dis 46: 212-219.
163. Ryan TM, Behringer RR, Martin NC, Townes TM, Palmiter RD, Brinster RL. 1989. A single erythroid-spe-cific DNase I super-hypersensitive site activates high levels of human β-globin gene expression in transgenic mice. Genes Dev 3: 314-323.
164. Sangerman J, Lee MS, Yao X, Oteng E, Hsiao CH, Li W, Zein S, Ofori-Acquah SF, Pace BS. 2006. Mechanism for fetal hemoglobin induction by histone deacetylase inhibitors involves γ-globin activation by CREB1 and ATF-2. Blood 108: 3590-3599.
165. Sankaran VG, Orkin SH. 2013. The switch from fetal to adult hemoglobin. Cold Spring Harb Perspeet Med 3: a011643.
166. Sankaran VG, Menne TF, Xu J, Akie TE, Lettre G, Van Handel B, Mikkola HK, Hirschhorn JN, Cantor AB, Orkin SH. 2008. Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. Science 322: 1839-1842.
167. Sankaran VG, Xu J, Ragoczy T, Ippolito GC, Walkley CR, Maika SD, Fujiwara Y, Ito M, Groudine M, Bender MA, et al. 2009. Developmental and species-divergent globin switching are driven by BCL11A. Nature 460: 1093-1097.
168. Sankaran VG, Xu J, Orkin SH. 2010a. Advances in the understanding of haemoglobin switching. Br J Haematol 149: 181-194.
169. Sankaran VG, Xu J, Orkin SH. 2010b. Transcriptional silencing of fetal hemoglobin by BCL11A. Ann NY Acad Sci 1202: 64-68.
170. Sankaran VG, Menne TF, Scepanovic D, Vergilio JA, Ji P, Kim J, Thiru P, Orkin SH, Lander ES, Lodish HE 2011. MicroRNA-15a and-16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13. Proc Natl Acad Sci 108: 1519-1524.
171. Schoenfelder S, Sexton T, Chakalova L, Cope NF, Horton A, Andrews S, Kurukuti S, Mitchell JA, Umlauf D, Dimitrova DS, et al. 2010. Preferential associations between co-regulated genes reveal a transcriptional interac-tome in erythroid cells. Nat Genet 42: 53-61.
172. Simon MC, Pevny L, Wiles MV, Keller G, Costantini F, Orkin SH. 1992. Rescue of erythroid development in gene targeted GATA-1 mouse embryonic stem cells. Nat Genet 1:92-98.
173. Simpson RJ, Yi Lee SH, Bartle N, Sum EY, Visvader JE, Matthews JM, MacKay JP, Crossley M. 2004. A classic zinc finger from friend of GATA mediates an interaction with the coiled-coil of transforming acidic coiled-coil 3. JBiol Chem 279: 39789-39797.
174. Snow JW, Kim J, Currie CR, Xu J, Orkin SH. 2010a. Sumoy-lation regulates interaction of FOG1 with C-terminal-binding protein (CTBP). JBiol Chem 285:28064-28075.
175. Snow JW, Trowbridge JJ, Fujiwara T, Emambokus NE, Grass JA, Orkin SH, Bresnick EH. 2010b. A single cis element maintains repression of the key developmental regulator Gata2. PLoS Genet 6: el001103.
176. Snow JW, Trowbridge JJ, Johnson KD, Fujiwara T, Emambokus NE, Grass JA, Orkin SH, Bresnick EH. 2011. Context-dependent function of GATA sites in vivo. Blood 117:4769-4772.
177. Song SH, Hou C, Dean A. 2007. A positive role for NLI/ Ldbl in long-range β-globin locus control region function. Mol Cell28: 810-822.
178. Souroullas GP, Salmon JM, Sablitzky F, Curtis DJ, Good-ell MA. 2009. Adult hematopoietic stem and progenitor cells require either Lyll or Sci for survival. Cell Stem Cell 4: 180-186.
179. Sripichai O, Kiefer CM, Bhanu NV, Tanno T, Noh SJ, Goh SH, Russell JE, Rognerud CL, Ou CN, Oneal PA, et al. 2009. Cytokine-mediated increases in fetal hemoglobin are associated with globin gene histone modification and transcription factor reprogramming. Blood 114: 2299-2306.
180. Stamatoyannopoulos JA, Goodwin A, Joyce T, Lowrey CH. 1995. NF-E2 and GATA binding motifs are required for the formation of DNase I hypersensitive site 4 of the human β-globin locus control region. EMBO J 14: 106-116.
181. Stumpf M, Waskow C, Krotschel M, van Essen D, Rodriguez P, Zhang X, Guyot B, Roeder RG, Borggrefe T 2006. The mediator complex functions as a coactivator for GATA-1 in erythropoiesis via subunit Medl/ TRAP220. Proc Natl Acad Sci 103: 18504-18509.
182. Stumpf M, Yue X, Schmitz S, Luche H, Reddy JK, Borggrefe T 2010. Specific erythroid-lineage defect in mice conditionally deficient for mediator subunit Medl. Proc Natl Acad Sci 107: 21541-21546.
183. Sugiyama D, Tanaka M, Kitajima K, Zheng J, Yen H, Murotani T, Yamatodani A, Nakano T 2008. Differential context-dependent effects of friend of GATA-1 (FOG-1) on mast-cell development and differentiation. Blood 111: 1924-1932.
184. Svensson EC, Tufts RL, Polk CE, Leiden JM. 1999. Molecular cloning of FOG-2: A modulator of transcription factor GATA-4 in cardiomyocytes. Proc Natl Acad Sci 96: 956-961.
185. Tanabe O, Katsuoka F, Campbell AD, Song W, Yamamoto M, Tanimoto K, Engel JD. 2002. An embryonic/fetal β-type globin gene repressor contains a nuclear receptor TR2/ TR4 heterodimer. EMBO J 21: 3434-3442.
186. Tanabe O, McPhee D, Kobayashi S, Shen Y, Brandt W, Jiang X, Campbell AD, Chen YT, Chang C, Yamamoto M, et al. 2007. Embryonic and fetal β-globin gene repression by the orphan nuclear receptors, TR2 and TR4. EMBO J 26: 2295-2306.
187. Tevosian SG, Deconinck AE, Cantor AB, Rieff HI, Fujiwara Y, Corfas G, Orkin SH. 1999. FOG-2: A novel GATA-family cofactor related to multitype zinc-finger proteins Friend of GATA-1 and U-shaped. Proc Natl Acad Sci 96: 950-955.
188. Tevosian SG, Deconinck AE, Tanaka M, Schinke M, Litovsky SH, Izumo S, Fujiwara Y, Orkin SH. 2000. FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium. Cell 101: 729-739.
189. Towatari M, Ciro M, Ottolenghi S, Tsuzuki S, Enver T. 2004. Involvement of mitogen-activated protein kinase in the cytokine-regulated phosphorylation of transcription factor GATA-1. HematolJ5: 262-272.
190. Tripic T, Deng W, Cheng Y, Zhang Y, Vakoc CR, Gregory GD, Hardison RC, Blobel GA. 2009. SCL and associated proteins distinguish active from repressive GATA transcription factor complexes. Blood 113: 2191-2201.
191. Tsai SF, Martin DI, Zon LI, D'Andrea AD, Wong GG, Orkin SH. 1989. Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature 339: 446-451.
192. Tsai FY, Keller G, Kuo FC, Weiss M, Chen J, Rosenblatt M, Alt FW, Orkin SH. 1994. An early haematopoietic defect in mice lacking the transcription factor GALA-2. Nature 371:221-226.
193. Tsang AP, Visvader JE, Turner CA, Fujiwara Y, Yu C, Weiss MJ, Crossley M, Orkin SH. 1997. FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation. Cell 90: 109-119.
194. Tsang AP, Fujiwara Y, Horn DB, Orkin SH. 1998. Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG. Genes Dev12: 1176-1188.
195. Tuan D, London IM. 1984. Mapping of DNase I-hypersen-sitive sites in the upstream DNA of human embryonic E-globin gene in K562 leukemia cells. Proc Natl Acad Sci 81:2718-2722.
196. Uda M, Galanello R, Sanna S, Lettre G, Sankaran VG, Chen W, Usala G, Busonero F, Maschio A, Albai G, et al. 2008. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of β-thalassemia. Proc Natl Acad Sci 105: 1620-1625.
197. Vakoc CR, Letting DL, Gheldof N, Sawado T, Bender MA, Groudine M, Weiss MJ, Dekker J, Blobel GA. 2005. Proximity among distant regulatory elements at the β-globin locus requires GATA-1 and FOG-1. Mol Cell 17:453-462.
198. Vyas P, Ault K, Jackson CW, Orkin SH, Shivdasani RA. 1999. Consequences of GATA-1 deficiency in megakaryocytes and platelets. Blood 93: 2867-2875.
199. Wahlberg K, Jiang J, Rooks H, Jawaid K, Matsuda F, Yamaguchi M, Lathrop M, Thein SL, Best S. 2009. The HBS1L-MYB intergenic interval associated with elevated HbF levels shows characteristics of a distal regulatory region in erythroid cells. Blood 114: 1254-1262.
200. Watanapokasin Y, Chuncharunee S, Sanmund D, Kong-nium W, Winichagoon P, Rodgers GP, Fucharoen S. 2005. In vivo and in vitro studies of fetal hemoglobin induction by hydroxyurea in β-thalassemia/hemoglobin E patients. Exp Hematol 33: 1486-1492.
201. Weatherall DJ. 2010. The inherited diseases of hemoglobin are an emerging global health burden. Blood 115: 4331-4336.
202. Wechsler J, Greene M, McDevitt MA, Anastasi JJEK, Le-Beau MM, Crispino JD. 2002. Acquired mutations in GATA-1 in the megakaryoblastic leukemia of Down syndrome. Nat Genet 32: 148-152.
203. Weinberg RS, Ji X, Sutton M, Perrine S, Galperin Y, Li Q, Liebhaber SA, Stamatoyannopoulos G, Atweh GE 2005. Butyrate increases the efficiency of translation of γ-globin mRNA. Blood 105: 1807-1809.
204. Weiss MJ, Orkin SH. 1995. Transcription factor GATA-1 permits survival and maturation of erythroid precursors by preventing apoptosis. Proc Natl Acad Sci 92: 9623-9627.
205. Weiss MJ, Keller G, Orkin SH. 1994. Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells. Genes Dev 8: 1184-1197.
206. Weiss MJ, Yu C, Orkin SH. 1997. Erythroid-cell-specific properties of transcription factor GATA-1 revealed by phenotypic rescue of a gene-targeted cell line. Mol Cell Biol 17: 1642-1651.
207. Welch JJ, Watts JA, Vakoc CR, Yao Y, Wang H, Hardison RC, Blobel GA, Chodosh LA, Weiss MJ. 2004. Global regulation of erythroid gene expression by transcription factor GATA-1. Blood 104: 3136-3147.
208. Wilber A, Nienhuis AW, Persons DA. 2011. Transcriptional regulation of fetal to adult hemoglobin switching: New therapeutic opportunities. Blood 117: 3945-3953.
209. Wilson DB, Dorfman DM, Orkin SH. 1990. A nonerythroid GATA-binding protein is required for function of the human preproendothelin-1 promoter in endothelial cells. Mol Cell Biol 10: 4854-4862.
210. Wozniak RJ, Keles S, Lugus JJ, Young KH, Boyer ME, Tran TM, Choi K, Bresnick EH. 2008. Molecular hallmarks of endogenous chromatin complexes containing master regulators of hematopoiesis. Mol Cell Biol 28: 6681-6694.
211. Wu W, Cheng Y, Keller CA, Ernst J, Kumar SA, Mishra T, Morrissey C, Dorman CM, Chen KB, Drautz D, et al. 2011. Dynamics of the epigenetic landscape during erythroid differentiation after GATA1 restoration. Genome Res 21: 1659-1671.
212. Xu J, Sankaran VG, Ni M, Menne TF, Puram RV, Kim W, Orkin SH. 2010. Transcriptional silencing of γ-globin by BCL11A involves long-range interactions and cooperation with SOX6. Genes Dev 24: 783-798.
213. Xu J, Peng C, Sankaran VG, Shao Z, Esrick EB, Chong BG, Ippolito GC, Fujiwara Y, Ebert BL, Tucker PW, et al. 2011. Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science 334: 993-996.
214. Yamamoto M, Ko LJ, Leonard MW, Beug H, Orkin SH, Engel JD. 1990. Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. Genes Devi: 1650-1662.
215. Yao X, Kodeboyina S, Liu L, Dzandu J, Sangerman J, Ofori-Acquah SF, Pace BS. 2009. Role of STAT3 and GATA-1 interactions in γ-globin gene expression. Exp Hematol 37: 889-900.
216. Yi Z, Cohen-Barak O, Hagiwara N, Kingsley PD, Fuchs DA, Erickson DT, Epner EM, Palis J, Brilliant MH. 2006. Sox6 directly silences ε-globin expression in definitive erythropoiesis. PLoS Genet 2: el4.
217. Yu C, Cantor AB, Yang H, Browne C, Wells RA, Fukiwara Y, Orkin SH. 2002. Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. J Exp Med 195: 1387-1395.
218. Yu YL, Chiang YJ, Chen YC, Papetti M, Juo CG, Skoult-chi AI, Yen JJ. 2005. MAPK-mediated phosphorylation of GATA-1 promotes Bcl-XL expression and cell survival. JBiol Chem 280: 29533-29542.
219. Yu M, Riva L, Xie H, Schindler Y, Moran TB, Cheng Y, Yu D, Hardison R, Weiss MJ, Orkin SH, et al. 2009. Insights into GATA-1-mediated gene activation versus repression via genome-wide chromatin occupancy analysis. Mol Cell 36: 682-695.
220. Yu Y, Wang J, Khaled W, Burke S, Li P, Chen X, Yang W, Jenkins NA, Copeland NG, Zhang S, et al. 2012. Bell la is essential for lymphoid development and negatively regulates p53. J Exp Med 209: 2467-2483.
221. Zhao W, Kitidis C, Fleming MD, Lodish HF, Ghaffari S. 2006. Erythropoietin stimulates phosphorylation and activation of GATA-1 via the PI3-kinase/AKT signaling pathway. Blood 107: 907-915.
222. Zhou D, Pawlik KM, Ren J, Sun CW, Townes TM. 2006. Differential binding of erythroid Krupple-like factor to embryonic/fetal globin gene promoters during development. JBiol Chem 281: 16052-16057.
223. Zhou D, Liu K, Sun CW, Pawlik KM, Townes TM. 2010. KLF1 regulates BCL11A expression and γ-to β-globin gene switching. Nat Genet 42: 742-744.
224. Zhu X, Wang Y, Pi W, Liu H, Wickrema A, Tuan D. 2012. NF-Y recruits both transcription activator and repressor to modulate tissue-and developmental stage-specific expression of human γ-globin gene. PLoS ONE7: e47175.
225. Zohren F, Souroullas GP, Luo M, Gerdemann U, Impe-rato MR, Wilson NK, Gottgens B, Lukov GL, Goodell MA. 2012. The transcription factor Lyl-1 regulates lymphoid specification and the maintenance of early T lineage progenitors. Nat Immunol 13: 761-769.
226. Zon LI, Tsai SF, Burgess S, Matsudaira P, Bruns GA, Orkin SH. 1990. The major human erythroid DNA-bind-ing protein (GF-1): Primary sequence and localization of the gene to the X chromosome. Proc Natl Acad Sci 87: 668-672.
227. Zon LI, Gurish MF, Stevens RL, Mather C, Reynolds DS, Austen KF, Orkin SH. 1991. GATA-binding transcription factors in mast cells regulate the promoter of the mast cell carboxypeptidase A gene. JBiol Chem 266:22948-22953.