The growth factor independence-1 transcription factor: New functions and new insights

Critical Reviews in Oncology/Hematology

Volumn 59, Issue 2, 2006, Pages 85-97

  Kazanjian, Avedis ^a   Gross, Eleanore A ^a   Grimes, H Leighton ^a  

^a University of Louisville School of Medicine   (United States)

Author keywords

Ash1; Growth factor independence 1; Hematopoiesis; Notch; Oncogene; Peripheral nervous system; Pulmonary neuroendocrine cells; T lymphopoiesis; Tumor suppressor

Indexed keywords

GROWTH FACTOR INDEPENDECE 1 TRANSCRIPTION FACTOR; ONCOPROTEIN; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

BLOOD; CELL DIFFERENTIATION; CELL FUNCTION; CELL MATURATION; CELL PROLIFERATION; CELL TYPE; CYTOKINE PRODUCTION; GENE OVEREXPRESSION; GENE TARGETING; HEMATOPOIESIS; HEMATOPOIETIC STEM CELL; HUMAN; LEUKEMIA; LEUKEMOGENESIS; LUNG SMALL CELL CANCER; LYMPHOPOIESIS; MOLONEY LEUKEMIA ONCOVIRUS; MUTAGENESIS; MUTATION; MYELOPOIESIS; NEUROENDOCRINE SYSTEM; NEUROSECRETORY CELL; NEUTROPENIA; NEUTROPHIL; NONHUMAN; ONCOGENE; PERIPHERAL NERVOUS SYSTEM; PHENOTYPE; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN INTERACTION; REVIEW; SENSORY NERVE CELL; SENSORY SYSTEM; TRANSCRIPTION REGULATION; TUMOR GROWTH; TUMOR SUPPRESSOR GENE;

ANIMALS; DNA-BINDING PROTEINS; HEMATOPOIESIS; HUMANS; MICE; NEURONS, AFFERENT; NEUROSECRETORY SYSTEMS; NEUTROPENIA; ONCOGENE PROTEINS; ORGAN SPECIFICITY; TRANSCRIPTION FACTORS; TUMOR SUPPRESSOR PROTEINS;

EID: 33746195568     PISSN: 10408428     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.critrevonc.2006.02.002     Document Type: Review

References (102)

1. Nolo R., Abbott L.A., and Bellen H.J. Senseless, a Zn finger transcription factor, is necessary and sufficient for sensory organ development in Drosophila. Cell 102 (2000) 349-362
2. Hock H., Hamblen M.J., Rooke H.M., et al. Intrinsic requirement for zinc finger transcription factor gfi-1 in neutrophil differentiation. Immunity 18 (2003) 109-120
3. Karsunky H., Zeng H., Schmidt T., et al. Inflammatory reactions and severe neutropenia in mice lacking the transcriptional repressor Gfi1. Nat Genet 30 (2002) 295-300
4. Yucel R., Karsunky H., Klein-Hitpass L., and Moroy T. The transcriptional repressor Gfi1 affects development of early, uncommitted c-Kit+ T cell progenitors and CD4/CD8 lineage decision in the thymus. J Exp Med 197 (2003) 831-844
5. Hock H., Hamblen M.J., Rooke H.M., et al. Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells. Nature 431 (2004) 1002-1007
6. Zeng H., Yucel R., Kosan C., Klein-Hitpass L., and Moroy T. Transcription factor Gfi1 regulates self-renewal and engraftment of hematopoietic stem cells. EMBO J 23 (2004) 4116-4125
7. Wallis D., Hamblen M., Zhou Y., et al. The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival. Development 130 (2003) 221-232
8. Yang Z., Ding K., Pan L., Deng M., and Gan L. Math5 determines the competence state of retinal ganglion cell progenitors. Dev Biol 264 (2003) 240-254
9. Kazanjian A., Wallis D., Au N., et al. Growth factor independence-1 is expressed in primary human neuroendocrine lung carcinomas and mediates the differentiation of murine pulmonary neuroendocrine cells. Cancer Res 64 (2004) 6874-6882
10. Person R.E., Li F.Q., Duan Z., et al. Gfi1 proto-oncogene mutation causes human neutropenia and targets neutrophil elastase. Nat Genet 34 (2003) 308-312
11. Lazo P.A., Klein-Szanto A.J., and Tsichlis P.N. T-cell lymphoma lines derived from rat thymomas induced by Moloney murine leukemia virus: phenotypic diversity and its implications. J Virol 64 (1990) 3948-3959
12. Gilks C.B., Bear S.E., Grimes H.L., and Tsichlis P.N. Progression of interleukin-2 (IL-2)-dependent rat T cell lymphoma lines to IL-2-independent growth following activation of a gene (Gfi-1) encoding a novel zinc finger protein. Mol Cell Biol 13 (1993) 1759-1768
13. Grimes H.L., Chan T.O., Zweidler-McKay P.A., Tong B., and Tsichlis P.N. The Gfi-1 proto-oncoprotein contains a novel transcriptional repressor domain, SNAG, and inhibits G1 arrest induced by interleukin-2 withdrawal. Mol Cell Biol 16 (1996) 6263-6272
14. Zornig M., Schmidt T., Karsunky H., Grzeschiczek A., and Moroy T. Zinc finger protein GFI-1 cooperates with myc and pim-1 in T-cell lymphomagenesis by reducing the requirements for IL-2. Oncogene 12 (1996) 1789-1801
15. Scheijen B., Jonkers J., Acton D., and Berns A. Characterization of pal-1, a common proviral insertion site in murine leukemia virus-induced lymphomas of c-myc and Pim-1 transgenic mice. J Virol 71 (1997) 9-16
16. Schmidt T., Zornig M., Beneke R., and Moroy T. MoMuLV proviral integrations identified by Sup-F selection in tumors from infected myc/pim bitransgenic mice correlate with activation of the gfi-1 gene. Nucleic Acids Res 24 (1996) 2528-2534
17. Liao X., Tang Y., Chattopadhyay S.K., Hartley J.W., and Morse H.C. Upregulation of Gfi-1, a gene involved in IL-2-independent growth of T cells, in a murine retrovirus-induced immunodeficiency syndrome. In Vivo 11 (1997) 9-12
18. Berns A., van der Lugt N., Alkema M., et al. Mouse model systems to study multistep tumorigenesis. Cold Spring Harb Symp Quant Biol 59 (1994) 435-447
19. Liao X., Buchberg A.M., Jenkins N.A., and Copeland N.G. Evi-5, a common site of retroviral integration in AKXD T-cell lymphomas, maps near Gfi-1 on mouse chromosome 5. J Virol 69 (1995) 7132-7137
20. Akagi K., Suzuki T., Stephens R.M., Jenkins N.A., and Copeland N.G. RTCGD: retroviral tagged cancer gene database. Nucleic Acids Res 32 (2004) D523-D527
21. Shin M.S., Fredrickson T.N., Hartley J.W., Suzuki T., Agaki K., and Morse III H.C. High-throughput retroviral tagging for identification of genes involved in initiation and progression of mouse splenic marginal zone lymphomas. Cancer Res 64 (2004) 4419-4427
22. Doan L.L., Kitay M.K., Yu Q., et al. Growth factor independence-1B expression leads to defects in T cell activation, IL-7 receptor alpha expression, and T cell lineage commitment. J Immunol 170 (2003) 2356-2366
23. Schmidt T., Karsunky H., Gau E., Zevnik B., Elsasser H.P., and Moroy T. Zinc finger protein GFI-1 has low oncogenic potential but cooperates strongly with pim and myc genes in T-cell lymphomagenesis. Oncogene 17 (1998) 2661-2667
24. Bell D.W., Taguchi T., Jenkins N.A., et al. Chromosomal localization of a gene, GF1, encoding a novel zinc finger protein reveals a new syntenic region between man and rodents. Cytogenet Cell Genet 70 (1995) 263-267
25. Roberts T., and Cowell J.K. Cloning of the human Gfi-1 gene and its mapping to chromosome region 1p22. Oncogene 14 (1997) 1003-1005
26. Berns A., Mikkers H., Krimpenfort P., Allen J., Scheijen B., and Jonkers J. Identification and characterization of collaborating oncogenes in compound mutant mice. Cancer Res 59 (1999) 1773s-1777s
27. Tong B., Grimes H.L., Yang T.Y., et al. The Gfi-1B proto-oncoprotein represses p21WAF1 and inhibits myeloid cell differentiation. Mol Cell Biol 18 (1998) 2462-2473
28. Alkema M.J., Jacobs H., van L.M., and Berns A. Pertubation of B and T cell development and predisposition to lymphomagenesis in Emu Bmi1 transgenic mice require the Bmi1 RING finger. Oncogene 15 (1997) 899-910
29. van Lohuizen M., Verbeek S., Scheijen B., Wientjens E., van der Gulden H., and Berns A. Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging. Cell 65 (1991) 737-752
30. Haupt Y., Alexander W.S., Barri G., Klinken S.P., and Adams J.M. Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice. Cell 65 (1991) 753-763
31. Alkema M.J., van der Lugt N.M., Bobeldijk R.C., Berns A., and van L.M. Transformation of axial skeleton due to overexpression of bmi-1 in transgenic mice. Nature 374 (1995) 724-727
32. Jacobs J.J., Kieboom K., Marino S., DePinho R.A., and van Lohuizen M. The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature 397 (1999) 164-168
33. Jacobs J.J., Scheijen B., Voncken J.W., Kieboom K., Berns A., and van Lohuizen M. Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc- induced apoptosis via INK4a/ARF. Genes Dev 13 (1999) 2678-2690
34. Juin P., Hueber A.O., Littlewood T., and Evan G. c-Myc-induced sensitization to apoptosis is mediated through cytochrome c release. Genes Dev 13 (1999) 1367-1381
35. Grimes H.L., Gilks C.B., Chan T.O., Porter S., and Tsichlis P.N. The Gfi-1 protooncoprotein represses Bax expression and inhibits T-cell death. Proc Natl Acad Sci USA 93 (1996) 14569-14573
36. Karsunky H., Mende I., Schmidt T., and Moroy T. High levels of the onco-protein Gfi-1 accelerate T-cell proliferation and inhibit activation induced T-cell death in Jurkat T-cells. Oncogene 21 (2002) 1571-1579
37. Zweidler-McKay P.A., Grimes H.L., Flubacher M.M., and Tsichlis P.N. Gfi-1 encodes a nuclear zinc finger protein that binds DNA and functions as a transcriptional repressor. Mol Cell Biol 16 (1996) 4024-4034
38. Batlle E., Sancho E., Franci C., et al. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2 (2000) 84-89
39. Nakakura E.K., Watkins D.N., Schuebel K.E., et al. Mammalian Scratch: a neural-specific Snail family transcriptional repressor. Proc Natl Acad Sci USA 98 (2001) 4010-4015
40. Breslin M.B., Zhu M., Notkins A.L., and Lan M.S. Neuroendocrine differentiation factor, IA-1, is a transcriptional repressor and contains a specific DNA-binding domain: identification of consensus IA-1 binding sequence. Nucleic Acids Res 30 (2002) 1038-1045
41. Ayyanathan K., Fredericks W.J., Berking C., et al. Hormone-dependent tumor regression in vivo by an inducible transcriptional repressor directed at the PAX3-FKHR oncogene. Cancer Res 60 (2000) 5803-5814
42. McGhee L., Bryan J., Elliot L., et al. Gfi1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins and represses transcription using a TSA-sensitive mcehanism. J Cell Biochem 89 (2003) 1005-1018
43. Amann J.M., Nip J., Strom D.K., et al. ETO, a target of t(8; 21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain. Mol Cell Biol 21 (2001) 6470-6483
44. Venezia T.A., Merchant A.A., Ramos C.A., et al. Molecular signatures of proliferation and quiescence in hematopoietic stem cells. PLoS Biol 2 (2004) e301
45. Saleque S., Cameron S., and Orkin S.H. The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages. Genes Dev 16 (2002) 301-306
46. Duan Z., and Horwitz M. Targets of the transcriptional repressor oncoprotein Gfi-1. Proc Natl Acad Sci USA 100 (2003) 5932-5937
47. Vassen L., Fiolka K., Mahlmann S., and Moroy T. Direct transcriptional repression of the genes encoding the zinc-finger proteins Gfi1b and Gfi1 by Gfi1b. Nucleic Acids Res 33 (2005) 987-998
48. Doan L.L., Porter S.D., Duan Z., et al. Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells. Nucleic Acids Res 32 (2004) 2508-2519
49. Yucel R., Kosan C., Heyd F., and Moroy T. Gfi1:GFP knock-in mutant reveals differential expression and auto-regulation of the gene growth factor independence 1 (Gfi1) during lymphocyte development. J Biol Chem 279 (2004) 40906-40917
50. Cheng T., Rodrigues N., Shen H., et al. Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 287 (2000) 1804-1808
51. Akaishi H., Takeda K., Kaisho T., et al. Defective IL-2-mediated IL-2 receptor alpha chain expression in Stat3-deficient T lymphocytes. Int Immunol 10 (1998) 1747-1751
52. Takeda K., Kaisho T., Yoshida N., Takeda J., Kishimoto T., and Akira S. Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis: generation and characterization of T cell-specific Stat3-deficient mice. J Immunol 161 (1998) 4652-4660
53. Chung C.D., Liao J., Liu B., et al. Specific inhibition of Stat3 signal transduction by PIAS3. Science 278 (1997) 1803-1805
54. Rodel B., Tavassoli K., Karsunky H., et al. The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3. EMBO J 19 (2000) 5845-5855
55. Bromberg J.F., Wrzeszczynska M.H., Devgan G., et al. Stat3 as an oncogene. Cell 98 (1999) 295-303
56. Zhu J., Guo L., Min B., et al. Growth factor independent-1 induced by IL-4 regulates Th2 cell proliferation. Immunity 16 (2002) 733-744
57. Schmidt T., Karsunky H., Rodel B., Zevnik B., Elsasser H.P., and Moroy T. Evidence implicating Gfi-1 and Pim-1 in pre-T-cell differentiation steps associated with beta-selection. EMBO J 17 (1998) 5349-5359
58. Park J.H., Yu Q., Erman B., et al. Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival. Immunity 21 (2004) 289-302
59. Friedman A.D. Transcriptional regulation of granulocyte and monocyte development. Oncogene 21 (2002) 3377-3390
60. Horwitz M., Benson K.F., Duan Z., et al. Role of neutrophil elastase in bone marrow failure syndromes: molecular genetic revival of the chalone hypothesis. Curr Opin Hematol 10 (2003) 49-54
61. Zhang D.E., Zhang P., Wang N.D., Hetherington C.J., Darlington G.J., and Tenen D.G. Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha-deficient mice. Proc Natl Acad Sci USA 94 (1997) 569-574
62. Yamanaka R., Barlow C., Lekstrom-Himes J., et al. Impaired granulopoiesis, myelodysplasia, and early lethality in CCAAT/enhancer binding protein epsilon-deficient mice. Proc Natl Acad Sci USA 94 (1997) 13187-13192
63. Scott E.W., Simon M.C., Anastasi J., and Singh H. Requirement of transcription factor Pu.1 in the development of multiple hematopoietic lineages. Science 265 (1994) 1573-1577
64. McKercher S.R., Torbett B.E., Anderson K.L., et al. Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. EMBO J 15 (1996) 5647-5658
65. Koh K.R., Janz M., Mapara M.Y., et al. Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis. Blood 105 (2004) 3833-3840
66. Modi W.S., Dean M., Seuanez H.N., Mukaida N., Matsushima K., and O'Brien S.J. Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8) resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily. Hum Genet 84 (1990) 185-187
67. Dale D.C., Person R.E., Bolyard A.A., et al. Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. Blood 96 (2000) 2317-2322
68. Horwitz M., Benson K.F., Person R.E., Aprikyan A.G., and Dale D.C. Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. Nat Genet 23 (1999) 433-436
69. Rathinam C., Geffers R., Yucel R., et al. The transcriptional repressor Gfi1 controls STAT3-dependent dendritic cell development and function. Immunity 22 (2005) 717-728
70. Laouar Y., Welte T., Fu X.Y., and Flavell R.A. STAT3 is required for Flt3L-dependent dendritic cell differentiation. Immunity 19 (2003) 903-912
71. Cameron S., Clark S.G., McDermott J.B., Aamodt E., and Horvitz H.R. PAG-3, a Zn-finger transcription factor, determines neuroblast fate in C. elegans. Development 129 (2002) 1763-1774
72. Frankfort B.J., Nolo R., Zhang Z., Bellen H., and Mardon G. Senseless repression of rough is required for R8 photoreceptor differentiation in the developing Drosophila eye. Neuron 32 (2001) 403-414
73. Jafar-Nejad H., Acar M., Nolo R., et al. Senseless acts as a binary switch during sensory organ precursor selection. Genes Dev 17 (2003) 2966-2978
74. Jia Y., Xie G., and Aamodt E. pag-3, a Caenorhabditis elegans gene involved in touch neuron gene expression and coordinated movement. Genetics 142 (1996) 141-147
75. Bermingham N.A., Hassan B.A., Price S.D., et al. Math1: an essential gene for the generation of inner ear hair cells. Science 284 (1999) 1837-1841
76. Chen Z.Y., and Corey D.P. An inner ear gene expression database. J Assoc Res Otolaryngol 3 (2002) 140-148
77. Erkman L., McEvilly R.J., Luo L., et al. Role of transcription factors Brn-3.1 and Brn-3. 2 in auditory and visual system development. Nature 381 (1996) 603-606
78. Xiang M., Gan L., Li D., et al. Essential role of POU-domain factor Brn-3c in auditory and vestibular hair cell development. Proc Natl Acad Sci USA 94 (1997) 9445-9450
79. Hertzano R., Montcouquiol M., Rashi-Elkeles S., et al. Transcription profiling of inner ears from Pou4f3(ddl/ddl) identifies Gfi1 as a target of the Pou4f3 deafness gene. Hum Mol Genet 13 (2004) 2143-2153
80. Ito T. Differentiation and proliferation of pulmonary neuroendocrine cells. Prog Histochem Cytochem 34 (1999) 247-322
81. Lauweryns J.M., and Van R.L. Immunocytochemical localization of aromatic L-amino acid decarboxylase in human, rat, and mouse bronchopulmonary and gastrointestinal endocrine cells. J Histochem Cytochem 36 (1988) 1181-1186
82. Fu X.W., Nurse C.A., Wong V., and Cutz E. Hypoxia-induced secretion of serotonin from intact pulmonary neuroepithelial bodies in neonatal rabbit. J Physiol 539 (2002) 503-510
83. Cutz E., and Jackson A. Neuroepithelial bodies as airway oxygen sensors. Respir Physiol 115 (1999) 201-214
84. Neuhuber W.L. Lung sensors: complex functions require complex structures. Am J Respir Cell Mol Biol 28 (2003) 265-266
85. Ito T., Udaka N., Yazawa T., et al. Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium. Development 127 (2000) 3913-3921
86. Borges M., Linnoila R.I., van de Velde H.J., et al. An achaete-scute homologue essential for neuroendocrine differentiation in the lung. Nature 386 (1997) 852-855
87. Younossian A.B., Brundler M.A., and Totsch M. Feasibility of the new WHO classification of pulmonary neuroendocrine tumours. Swiss Med Wkly 132 (2002) 535-540
88. Wistuba I.I., Gazdar A.F., and Minna J.D. Molecular genetics of small cell lung carcinoma. Semin Oncol 28 (2001) 3-13
89. Koutsami M.K., Doussis-Anagnostopoulou I., Papavassiliou A.G., and Gorgoulis V.G. Genetic and molecular coordinates of neuroendocrine lung tumors, with emphasis on small-cell lung carcinomas. Mol Med 8 (2002) 419-436
90. Linnoila R.I., Zhao B., DeMayo J.L., et al. Constitutive achaete-scute homologue-1 promotes airway dysplasia and lung neuroendocrine tumors in transgenic mice. Cancer Res 60 (2000) 4005-4009
91. Ito T., Udaka N., Ikeda M., Yazawa T., Kageyama R., and Kitamura H. Significance of proneural basic helix-loop-helix transcription factors in neuroendocrine differentiation of fetal lung epithelial cells and lung carcinoma cells. Histol Histopathol 16 (2001) 335-343
92. Chen H., Biel M.A., Borges M.W., et al. Tissue-specific expression of human achaete-scute homologue-1 in neuroendocrine tumors: transcriptional regulation by dual inhibitory regions. Cell Growth Differ 8 (1997) 677-686
93. Taipale J., and Beachy P.A. The Hedgehog and Wnt signalling pathways in cancer. Nature 411 (2001) 349-354
94. Sriuranpong V., Borges M.W., Ravi R.K., et al. Notch signaling induces cell cycle arrest in small cell lung cancer cells. Cancer Res 61 (2001) 3200-3205
95. Sriuranpong V., Borges M.W., Strock C.L., et al. Notch signaling induces rapid degradation of achaete-scute homolog 1. Mol Cell Biol 22 (2002) 3129-3139
96. Pear W.S., and Radtke F. Notch signaling in lymphopoiesis. Semin Immunol 15 (2003) 69-79
97. Dwivedi P.P., Anderson P.H., Omdahl J.L., Grimes H.L., Morris H.A., and May B.K. Identification of growth factor independent-1 (GFI1) as a repressor of 25-hydroxyvitamin D 1-alpha hydroxylase (CYP27B1) gene expression in human prostate cancer cells. Endocr Relat Cancer 12 (2005) 351-365
98. Zhuang S.H., and Burnstein K.L. Antiproliferative effect of 1alpha, 25-dihydroxyvitamin D3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation. Endocrinology 139 (1998) 1197-1207
99. Blutt S.E., McDonnell T.J., Polek T.C., and Weigel N.L. Calcitriol-induced apoptosis in LNCaP cells is blocked by overexpression of Bcl-2. Endocrinology 141 (2000) 10-17
100. Jones G., Strugnell S.A., and DeLuca H.F. Current understanding of the molecular actions of vitamin D. Physiol Rev 78 (1998) 1193-1231
101. Hsu J.Y., Feldman D., McNeal J.E., and Peehl D.M. Reduced 1alpha-hydroxylase activity in human prostate cancer cells correlates with decreased susceptibility to 25-hydroxyvitamin D3-induced growth inhibition. Cancer Res 61 (2001) 2852-2856
102. Duan Z., Zarebski A., Montoya-Durango D., Grimes H.L., and Horwitz M. Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1. Mol Cell Biol 25 (2005) 10338-10351