Cytokine-induced megakaryocytic differentiation is regulated by genome-wide loss of a uSTAT transcriptional program

EMBO Journal

Volumn 35, Issue 6, 2016, Pages 580-594

  Park, Hyun Jung ^a,b   Li, Juan ^a,b   Hannah, Rebecca ^a,b   Biddie, Simon ^a,b   Leal Cervantes, Ana I ^a,b   Kirschner, Kristina ^a,b   Flores Santa Cruz, David ^a,b   Sexl, Veronika ^c   Göttgens, Berthold ^a,b   Green, Anthony R ^a,b,d  

^a WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF VETERINARY MEDICINE   (Austria)

^d ADDENBROOKE S HOSPITAL   (United Kingdom)

Author keywords

cytokine; differentiation; haematopoiesis; JAK STAT; megakaryocyte

Indexed keywords

CYTOKINE; STAT5 PROTEIN; STAT5A PROTEIN; STAT5B PROTEIN; THROMBOPOIETIN; TRANSCRIPTION FACTOR CTCF; TRANSCRIPTION FACTOR ERG; TRANSCRIPTION FACTOR FLI 1; TRANSCRIPTION FACTOR GATA 1; TRANSCRIPTION FACTOR GATA 2; TRANSCRIPTION FACTOR RUNX1; TRANSCRIPTION FACTOR TAL1;

ANIMAL CELL; APOPTOSIS; ARTICLE; BINDING SITE; CELL ACTIVATION; CELL DIFFERENTIATION; CELL PROLIFERATION; CELLULAR DISTRIBUTION; CHROMATIN IMMUNOPRECIPITATION; COMPARATIVE STUDY; CONTROLLED STUDY; GENE MAPPING; GENE TARGETING; GENETIC ASSOCIATION; HEMATOPOIETIC STEM CELL; MEGAKARYOCYTE; MEGAKARYOPOIESIS; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; TRANSCRIPTION REGULATION; ANIMAL; C57BL MOUSE; CELL CULTURE; DRUG EFFECTS; GENE EXPRESSION REGULATION; METABOLISM; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN PROCESSING;

ANIMALS; CELL DIFFERENTIATION; CELL PROLIFERATION; CELLS, CULTURED; GENE EXPRESSION REGULATION; MEGAKARYOCYTES; MICE, INBRED C57BL; PHOSPHORYLATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; STAT5 TRANSCRIPTION FACTOR; THROMBOPOIETIN;

EID: 84961806518     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.15252/embj.201592383     Document Type: Article

References (79)

1. Alexander WS, Roberts AW, Nicola NA, Li R, Metcalf D, (1996) Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietic receptor c-Mpl. Blood 87: 2162-2170
2. Anders S, Huber W, (2010) Differential expression analysis for sequence count data. Genome Biol 11: R106
3. Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, Ren J, Li WW, Noble WS, (2009) MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res 37: W202-W208
4. Bailey TL, Machanick P, (2012) Inferring direct DNA binding from ChIP-seq. Nucleic Acids Res 40: e128
5. Bunting S, Widmer R, Lipari T, Rangell L, Steinmetz H, Carver-Moore K, Moore MW, Keller GA, de Sauvage FJ, (1997) Normal platelets and megakaryocytes are produced in vivo in the absence of thrombopoietin. Blood 90: 3423-3429
6. Calero-Nieto FJ, Ng FS, Wilson NK, Hannah R, Moignard V, Leal-Cervantes AI, Jimenez-Madrid I, Diamanti E, Wernisch L, Gottgens B, (2014) Key regulators control distinct transcriptional programmes in blood progenitor and mast cells. EMBO J 33: 1212-1226
7. Chatterjee-Kishore M, Wright KL, Ting JP, Stark GR, (2000) How Stat1 mediates constitutive gene expression: a complex of unphosphorylated Stat1 and IRF1 supports transcription of the LMP2 gene. EMBO J 19: 4111-4122
8. Chen E, Staudt LM, Green AR, (2012) Janus kinase deregulation in leukemia and lymphoma. Immunity 36: 529-541
9. Cheon H, Yang J, Stark GR, (2011) The functions of signal transducers and activators of transcriptions 1 and 3 as cytokine-inducible proteins. J Interferon Cytokine Res 31: 33-40
10. Cross MA, Enver T, (1997) The lineage commitment of haemopoietic progenitor cells. Curr Opin Genet Dev 7: 609-613
11. Cui Y, Riedlinger G, Miyoshi K, Tang W, Li C, Deng CX, Robinson GW, Hennighausen L, (2004) Inactivation of Stat5 in mouse mammary epithelium during pregnancy reveals distinct functions in cell proliferation, survival, and differentiation. Mol Cell Biol 24: 8037-8047
12. Cui X, Zhang L, Luo J, Rajasekaran A, Hazra S, Cacalano N, Dubinett SM, (2007) Unphosphorylated STAT6 contributes to constitutive cyclooxygenase-2 expression in human non-small cell lung cancer. Oncogene 26: 4253-4260
13. st edn. San Diego: Academic Press/Elsevier
14. Davidson EH, (2010) Emerging properties of animal gene regulatory networks. Nature 468: 911-920
15. Dawson MA, Bannister AJ, Gottgens B, Foster SD, Bartke T, Green AR, Kouzarides T, (2009) JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature 461: 819-822
16. Dawson MA, Foster SD, Bannister AJ, Robson SC, Hannah R, Wang X, Xhemalce B, Wood AD, Green AR, Gottgens B, Kouzarides T, (2012) Three distinct patterns of histone H3Y41 phosphorylation mark active genes. Cell Rep 2: 470-477
17. Dumon S, Walton DS, Volpe G, Wilson N, Dasse E, Del Pozzo W, Landry JR, Turner B, O'Neill LP, Gottgens B, Frampton J, (2012) Itga2b regulation at the onset of definitive hematopoiesis and commitment to differentiation. PLoS ONE 7: e43300
18. Enver T, Greaves M, (1998) Loops, lineage, and leukemia. Cell 94: 9-12
19. Forsberg EC, Downs KM, Bresnick EH, (2000) Direct interaction of NF-E2 with hypersensitive site 2 of the beta-globin locus control region in living cells. Blood 96: 334-339
20. Fox N, Priestley G, Papayannopoulou T, Kaushansky K, (2002) Thrombopoietin expands hematopoietic stem cells after transplantation. J Clin Invest 110: 389-394
21. Furqan M, Akinleye A, Mukhi N, Mittal V, Chen Y, Liu D, (2013) STAT inhibitors for cancer therapy. J Hematol Oncol 6: 90
22. Goldberg L, Tijssen MR, Birger Y, Hannah RL, Kinston SJ, Schutte J, Beck D, Knezevic K, Schiby G, Jacob-Hirsch J, Biran A, Kloog Y, Marcucci G, Bloomfield CD, Aplan PD, Pimanda JE, Gottgens B, Izraeli S, (2013) Genome-scale expression and transcription factor binding profiles reveal therapeutic targets in transgenic ERG myeloid leukemia. Blood 122: 2694-2703
23. Griffiths DS, Li J, Dawson MA, Trotter MW, Cheng YH, Smith AM, Mansfield W, Liu P, Kouzarides T, Nichols J, Bannister AJ, Green AR, Gottgens B, (2011) LIF-independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease. Nat Cell Biol 13: 13-21
24. Gupta S, Stamatoyannopoulos JA, Bailey TL, Noble WS, (2007) Quantifying similarity between motifs. Genome Biol 8: R24
25. Gurney AL, Carver-Moore K, de Sauvage FJ, Moore MW, (1994) Thrombocytopenia in c-mpl-deficient mice. Science 265: 1445-1447
26. Hart A, Melet F, Grossfeld P, Chien K, Jones C, Tunnacliffe A, Favier R, Bernstein A, (2000) Fli-1 is required for murine vascular and megakaryocytic development and is hemizygously deleted in patients with thrombocytopenia. Immunity 13: 167-177
27. Hennighausen L, Robinson GW, (2008) Interpretation of cytokine signaling through the transcription factors STAT5A and STAT5B. Genes Dev 22: 711-721
28. Hirahara K, Onodera A, Villarino AV, Bonelli M, Sciume G, Laurence A, Sun HW, Brooks SR, Vahedi G, Shih HY, Gutierrez-Cruz G, Iwata S, Suzuki R, Mikami Y, Okamoto Y, Nakayama T, Holland SM, Hunter CA, Kanno Y, O'Shea JJ, (2015) Asymmetric action of STAT transcription factors drives transcriptional outputs and cytokine specificity. Immunity 42: 877-889
29. Hoelbl A, Kovacic B, Kerenyi MA, Simma O, Warsch W, Cui Y, Beug H, Hennighausen L, Moriggl R, Sexl V, (2006) Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation. Blood 107: 4898-4906
30. Kang K, Robinson GW, Hennighausen L, (2013) Comprehensive meta-analysis of Signal Transducers and Activators of Transcription (STAT) genomic binding patterns discerns cell-specific cis-regulatory modules. BMC Genom 14: 4
31. Kato Y, Iwama A, Tadokoro Y, Shimoda K, Minoguchi M, Akira S, Tanaka M, Miyajima A, Kitamura T, Nakauchi H, (2005) Selective activation of STAT5 unveils its role in stem cell self-renewal in normal and leukemic hematopoiesis. J Exp Med 202: 169-179
32. Kirito K, Kaushansky K, (2006) Transcriptional regulation of megakaryopoiesis: thrombopoietin signaling and nuclear factors. Curr Opin Hematol 13: 151-156
33. Kruse EA, Loughran SJ, Baldwin TM, Josefsson EC, Ellis S, Watson DK, Nurden P, Metcalf D, Hilton DJ, Alexander WS, Kile BT, (2009) Dual requirement for the ETS transcription factors Fli-1 and Erg in hematopoietic stem cells and the megakaryocyte lineage. Proc Natl Acad Sci USA 106: 13814-13819
34. Levy DE, Darnell JE Jr, (2002) Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol 3: 651-662
35. Liu X, Robinson GW, Wagner KU, Garrett L, Wynshaw-Boris A, Hennighausen L, (1997) Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev 11: 179-186
36. Loughran SJ, Kruse EA, Hacking DF, de Graaf CA, Hyland CD, Willson TA, Henley KJ, Ellis S, Voss AK, Metcalf D, Hilton DJ, Alexander WS, Kile BT, (2008) The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells. Nat Immunol 9: 810-819
37. McLean CY, Bristor D, Hiller M, Clarke SL, Schaar BT, Lowe CB, Wenger AM, Bejerano G, (2010) GREAT improves functional interpretation of cis-regulatory regions. Nat Biotechnol 28: 495-501
38. Metcalf D, (2008) Hematopoietic cytokines. Blood 111: 485-491
39. Moriggl R, Sexl V, Kenner L, Duntsch C, Stangl K, Gingras S, Hoffmeyer A, Bauer A, Piekorz R, Wang D, Bunting KD, Wagner EF, Sonneck K, Valent P, Ihle JN, Beug H, (2005) Stat5 tetramer formation is associated with leukemogenesis. Cancer Cell 7: 87-99
40. Ng AP, Loughran SJ, Metcalf D, Hyland CD, de Graaf CA, Hu Y, Smyth GK, Hilton DJ, Kile BT, Alexander WS, (2011) Erg is required for self-renewal of hematopoietic stem cells during stress hematopoiesis in mice. Blood 118: 2454-2461
41. Nora EP, Lajoie BR, Schulz EG, Giorgetti L, Okamoto I, Servant N, Piolot T, van Berkum NL, Meisig J, Sedat J, Gribnau J, Barillot E, Bluthgen N, Dekker J, Heard E, (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485: 381-385
42. Ong CT, Corces VG, (2014) CTCF: an architectural protein bridging genome topology and function. Nat Rev Genet 15: 234-246
43. Orkin SH, Zon LI, (2008) Hematopoiesis: an evolving paradigm for stem cell biology. Cell 132: 631-644
44. Osborn L, Kunkel S, Nabel GJ, (1989) Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci USA 86: 2336-2340
45. Paredes SH, Melgar MF, Sethupathy P, (2013) Promoter-proximal CCCTC-factor binding is associated with an increase in the transcriptional pausing index. Bioinformatics 29: 1485-1487
46. Pimkin M, Kossenkov AV, Mishra T, Morrissey CS, Wu W, Keller CA, Blobel GA, Lee D, Beer MA, Hardison RC, Weiss MJ, (2014) Divergent functions of hematopoietic transcription factors in lineage priming and differentiation during erythro-megakaryopoiesis. Genome Res 24: 1932-1944
47. Pinto do OP, Kolterud A, Carlsson L, (1998) Expression of the LIM-homeobox gene LH2 generates immortalized steel factor-dependent multipotent hematopoietic precursors. EMBO J 17: 5744-5756.
48. Pronk CJ, Rossi DJ, Mansson R, Attema JL, Norddahl GL, Chan CK, Sigvardsson M, Weissman IL, Bryder D, (2007) Elucidation of the phenotypic, functional, and molecular topography of a myeloerythroid progenitor cell hierarchy. Cell Stem Cell 1: 428-442
49. Sanjuan-Pla A, Macaulay IC, Jensen CT, Woll PS, Luis TC, Mead A, Moore S, Carella C, Matsuoka S, Bouriez Jones T, Chowdhury O, Stenson L, Lutteropp M, Green JC, Facchini R, Boukarabila H, Grover A, Gambardella A, Thongjuea S, Carrelha J, et al, (2013) Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy. Nature 502: 232-236
50. de Sauvage FJ, Carver-Moore K, Luoh SM, Ryan A, Dowd M, Eaton DL, Moore MW, (1996) Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin. J Exp Med 183: 651-656
51. Schepers H, Wierenga AT, Vellenga E, Schuringa JJ, (2012) STAT5-mediated self-renewal of normal hematopoietic and leukemic stem cells. JAKSTAT 1: 13-22
52. Schuringa JJ, Chung KY, Morrone G, Moore MA, (2004) Constitutive activation of STAT5A promotes human hematopoietic stem cell self-renewal and erythroid differentiation. J Exp Med 200: 623-635
53. Seitan VC, Faure AJ, Zhan Y, McCord RP, Lajoie BR, Ing-Simmons E, Lenhard B, Giorgetti L, Heard E, Fisher AG, Flicek P, Dekker J, Merkenschlager M, (2013) Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments. Genome Res 23: 2066-2077
54. Shi S, Calhoun HC, Xia F, Li J, Le L, Li WX, (2006) JAK signaling globally counteracts heterochromatic gene silencing. Nat Genet 38: 1071-1076
55. Shi S, Larson K, Guo D, Lim SJ, Dutta P, Yan SJ, Li WX, (2008) Drosophila STAT is required for directly maintaining HP1 localization and heterochromatin stability. Nat Cell Biol 10: 489-496
56. Shin H, Liu T, Manrai AK, Liu XS, (2009) CEAS: cis-regulatory element annotation system. Bioinformatics 25: 2605-2606
57. Shukla S, Kavak E, Gregory M, Imashimizu M, Shutinoski B, Kashlev M, Oberdoerffer P, Sandberg R, Oberdoerffer S, (2011) CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Nature 479: 74-79
58. Sofueva S, Yaffe E, Chan WC, Georgopoulou D, Vietri Rudan M, Mira-Bontenbal H, Pollard SM, Schroth GP, Tanay A, Hadjur S, (2013) Cohesin-mediated interactions organize chromosomal domain architecture. EMBO J 32: 3119-3129
59. Solar GP, Kerr WG, Zeigler FC, Hess D, Donahue C, de Sauvage FJ, Eaton DL, (1998) Role of c-mpl in early hematopoiesis. Blood 92: 4-10
60. Stadhouders R, Thongjuea S, Andrieu-Soler C, Palstra RJ, Bryne JC, van den Heuvel A, Stevens M, de Boer E, Kockx C, van der Sloot A, van den Hout M, van Ijcken W, Eick D, Lenhard B, Grosveld F, Soler E, (2012) Dynamic long-range chromatin interactions control Myb proto-oncogene transcription during erythroid development. EMBO J 31: 986-999
61. Stark GR, Darnell JE Jr, (2012) The JAK-STAT pathway at twenty. Immunity 36: 503-514
62. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP, (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102: 15545-15550
63. Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, Ihle JN, (1998) Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell 93: 841-850
64. Tursky ML, Beck D, Thoms JA, Huang Y, Kumari A, Unnikrishnan A, Knezevic K, Evans K, Richards LA, Lee E, Morris J, Goldberg L, Izraeli S, Wong JW, Olivier J, Lock RB, MacKenzie KL, Pimanda JE, (2015) Overexpression of ERG in cord blood progenitors promotes expansion and recapitulates molecular signatures of high ERG leukemias. Leukemia 29: 819-827
65. Udy GB, Towers RP, Snell RG, Wilkins RJ, Park SH, Ram PA, Waxman DJ, Davey HW, (1997) Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc Natl Acad Sci USA 94: 7239-7244
66. Vainchenker W, Constantinescu SN, (2013) JAK/STAT signaling in hematological malignancies. Oncogene 32: 2601-2613
67. Wang L, Feng Z, Wang X, Wang X, Zhang X, (2010) DEGseq: an R package for identifying differentially expressed genes from RNA-seq data. Bioinformatics 26: 136-138
68. Wang Y, Levy DE, (2012) Comparative evolutionary genomics of the STAT family of transcription factors. JAKSTAT 1: 23-33
69. Whitington T, Frith MC, Johnson J, Bailey TL, (2011) Inferring transcription factor complexes from ChIP-seq data. Nucleic Acids Res 39: e98
70. Wilson NK, Foster SD, Wang X, Knezevic K, Schutte J, Kaimakis P, Chilarska PM, Kinston S, Ouwehand WH, Dzierzak E, Pimanda JE, de Bruijn MF, Gottgens B, (2010) Combinatorial transcriptional control in blood stem/progenitor cells: genome-wide analysis of ten major transcriptional regulators. Cell Stem Cell 7: 532-544
71. Yamamoto R, Morita Y, Ooehara J, Hamanaka S, Onodera M, Rudolph KL, Ema H, Nakauchi H, (2013) Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells. Cell 154: 1112-1126
72. Yang J, Chatterjee-Kishore M, Staugaitis SM, Nguyen H, Schlessinger K, Levy DE, Stark GR, (2005) Novel roles of unphosphorylated STAT3 in oncogenesis and transcriptional regulation. Cancer Res 65: 939-947
73. Yang J, Liao X, Agarwal MK, Barnes L, Auron PE, Stark GR, (2007) Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFkappaB. Genes Dev 21: 1396-1408
74. Yang XP, Ghoreschi K, Steward-Tharp SM, Rodriguez-Canales J, Zhu J, Grainger JR, Hirahara K, Sun HW, Wei L, Vahedi G, Kanno Y, O'Shea JJ, Laurence A, (2011) Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat Immunol 12: 247-254
75. Yao Z, Cui Y, Watford WT, Bream JH, Yamaoka K, Hissong BD, Li D, Durum SK, Jiang Q, Bhandoola A, Hennighausen L, O'Shea JJ, (2006) Stat5a/b are essential for normal lymphoid development and differentiation. Proc Natl Acad Sci USA 103: 1000-1005
76. Yoshihara H, Arai F, Hosokawa K, Hagiwara T, Takubo K, Nakamura Y, Gomei Y, Iwasaki H, Matsuoka S, Miyamoto K, Miyazaki H, Takahashi T, Suda T, (2007) Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell 1: 685-697
77. Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, Nusbaum C, Myers RM, Brown M, Li W, Liu XS, (2008) Model-based analysis of ChIP-Seq (MACS). Genome Biol 9: R137
78. Zhu BM, Kang K, Yu JH, Chen W, Smith HE, Lee D, Sun HW, Wei L, Hennighausen L, (2012) Genome-wide analyses reveal the extent of opportunistic STAT5 binding that does not yield transcriptional activation of neighboring genes. Nucleic Acids Res 40: 4461-4472
79. Zuin J, Dixon JR, van der Reijden MI, Ye Z, Kolovos P, Brouwer RW, van de Corput MP, van de Werken HJ, Knoch TA, van IWF, Grosveld FG, Ren B, Wendt KS, (2014) Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells. Proc Natl Acad Sci USA 111: 996-1001