Skip to main content
PMC home page
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;9(1):103–112. doi: 10.1111/j.1582-4934.2005.tb00340.x

Important roles of reversible acetylation in the function of hematopoietic transcription factors

Xiaofang Huo 1, Junwu Zhang 1,✉
PMCID: PMC6741356  PMID: 15784168

Abstract

Hematopoiesis is a very complex process whose proper functioning requires the regulated action of a number of transcription factors. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) play significant roles in the regulation of hematopoietic transcription factors activity. Transcription factors such as GATA‐1, EKLF, NF‐E2, GATA‐1, PU.1 recruit HATs and HDACs to chromatin, leading to histone acetylation and deacetylation, that affect chromatin structure and result in gene expression changes. On the other hand, transcription factors themselves can be acetylated and deacetylated by HATs and HDACs, respectively. Consequently, some important functions of these transcription factors are influenced, including DNA binding, transcription activation, repressor activity and protein‐protein interactions. The regulation of hematopoietic transcription factors activity by HATs and HDACs may serve as a good model for studying how tissue‐specific and lineage‐specific gene expression is controlled through acetylation/deacetylation of histone/nonhistone proteins.

Keywords: histone acetyltransferases, histone deacetylases, hematopoietic transcription factor

References

  • 1. Buck S.W., Gallo C.M., and Smith J.S., Diversity in the Sir2 family of protein deacetylases, J. Leukoc. Biol., 75: 939–950, 2004. [DOI] [PubMed] [Google Scholar]
  • 2. Brownell J.E., Zhou J., Ranalli T., Ranalli T., Kobayashi R., Edmondson D.G., Roth S.Y., Allis C.D., Tetrahymena histone acetyltransferases A: a homolog to yeast Gcn5p linking histone acetylation to gene regulation, Cell, 84: 843–851, 1996. [DOI] [PubMed] [Google Scholar]
  • 3. Kawasaki H., Schiltz L., Chiu R., Itakura K., Taira K., Nakatani Y., Yokoyama K.K., ATF‐2 has intrinsic histone acetyltransferases activity which is modulated by phosphorylation, Nature, 405: 195–200, 2000. [DOI] [PubMed] [Google Scholar]
  • 4. Marmorstein T., Roth S.Y., Histone acetyltransferases: function, structure, and catalysis, Curr. Opin. Gene. Dev., 11: 155–161, 2001. [DOI] [PubMed] [Google Scholar]
  • 5. De Ruijter A.J.M., Van Gennip A.H., Caron N., Kemp S., Van Kuilenburg A.B.P., Histone deacetylases (HDACs): characterization of the classical HDAC family, Biochem. J., 370: 737–749, 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Blander G., Guarente L., The Sir2 family of protein deacetylases, Annu. Rev. Biochem., 73: 417–435, 2004. [DOI] [PubMed] [Google Scholar]
  • 7. Zon L.I., Tsai S., Burgess S., Matsudaira P., Bruns G., and Orkin S.H., The major human erythroid DNA‐binding protein (GF‐1): primary sequence and localization of the gene to the X chromosome, Proc. Natl. Acad. Sci. USA, 87: 668–672, 1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Yamamoto M., Takahashi S., Onodera K., Muraosa Y., Engel J.D., Upstream and downstream of erythroid transcription factor GATA‐1, Genes. Cell., 2: 107–115, 1997. [DOI] [PubMed] [Google Scholar]
  • 9. Weiss M.J., Keller G., Orkin S.H., Novel insights into mouse erythroid development revealed through in vitro differentiation of GATA‐1‐embryonic stem cells, Genes. Dev., 8: 1184–1197, 1994. [DOI] [PubMed] [Google Scholar]
  • 10. Weiss M.J., Orkin S.H., GATA transcription factors: key regulators of hematopoiesis, Exp. Hematol., 23: 99–107, 1995. [PubMed] [Google Scholar]
  • 11. Trainor C.D., Omichinski J.G., Vandergon T.L., Gronenborn A.M., Clore G.M., Felsenfeld G., A palindormic regulatory site within vertebrate GATA‐1 promoters requires both zinc fingers of the GATA‐1 DNA‐binding domain for high‐affinity interaction, Mol. Cell. Biol., 16: 2238–2247, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Boyes J., Byfield P., Nakatani Y., Vasily O., Regulation of activity of the transcription factor GATA‐1 by acetylation, Nature, 396: 594–598, 1998. [DOI] [PubMed] [Google Scholar]
  • 13. Hung H.L., Lau J., KIM A.Y., Weiss M.J., Blobel G.A., CREB‐binding protein acetylates hematopoietic transcription factor GATA‐1 at functionally important sites, Mol Cell Biol., 19: 3496–3505, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. Letting D.L., Rakowski C., Weiss M.J., Formation of a tissue‐specific histone acetylation pattern by the hematopoietic transcription factor GATA‐1, Mol. Cell. Biol., 23: 1334–1340, 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Johnson K.D., Grass J.A., Boyer M.E., Kiekhaefer C.M., Blobel G.A., Weiss M.J., Bresnick E.H., Cooperative activities of hematopoietic regulator recruit RNA polymerase II to a tissue‐specific chromatin domain, Proc. Natl. Acad. Sci. USA., 99: 11760–11765, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Kiekhaefer C.M., Grass J.A., Johnson K.D., Boyer M.E., Bresnick E.H., Hematopoietic‐specific activators establish an overlapping pattern of histone acetylation and methylation within a mammalian chromatin domain, Proc. Natl. Acad. Sci. USA., 99: 14309–14314, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Watamoto K., Towatari M., Ozawa Y., Miyata Y., Okamoto M., Abe A., Naoe T., Saito H., Altered interaction of HDAC5 with GATA‐1 during MEL cell differentiation, Oncogene, 22: 9176–9184, 2003. [DOI] [PubMed] [Google Scholar]
  • 18. Andrews N.C., Erjument‐Bromage H., Davidson M.B., Tempst P., Orkin S.H., Erythroid transcription factor NF‐E2 is a haematopoietic‐specific basic‐leucine zipper protein, Nature, 362: 722–728, 1993. [DOI] [PubMed] [Google Scholar]
  • 19. Andrews N.C., Kotkow K.J., Ney P.A., Erjument‐Bromage H., Tempst P., Orkin S.H., The ubiquitous subunit of erythroid transcription factor NF‐E2 is a small basic‐leucine zipper protein related to the v‐maf oncogene, Proc. Natl. Acad. Sci. USA., 90: 11488–92, 1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Hung H.L., Kim A.Y., Hong W., Rakowski C. Blobel G.A., Stimulation of NF‐E2 DNA binding by CREB‐binding protein (CBP)‐mediated acetylation, J. Biol. Chem., 276: 10715–10721, 2001. [DOI] [PubMed] [Google Scholar]
  • 21. Johnson, K.D. , Christensen, H.M. , Zhao B., Bresnick E.H., Distinct mechanism control RNA polymerase II recruitment to a tissue‐specific locus control region and a downstream promoter, Mol. Cell., 8: 465–471, 2001. [DOI] [PubMed] [Google Scholar]
  • 22. Sawado, T , Lgarashi K, Groudine, M. , Activation of beta‐major globin gene transcription is associated with recruitment of NF‐E2 to the beta‐globin LCR and gene promoter, Proc. Natl. Acad. Sci. USA., 98: 10226–10231, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Mosser E.A., Kasanov J.D., Forsberg E.C., Kay B.K., Ney P.A., Bresnick E.H., Physical and functional interactions between the transcription domain of the hematopoietic transcription factor NF‐E2 and WW domains, Biochemistry, 37: 13686–13695, 1998. [DOI] [PubMed] [Google Scholar]
  • 24. Kiekhaefer C.M., Boyer M.E., Johnson K.D., Bresnick E.H., A WW domain‐binding motif within the activation domain of the hematopoietic transcription factor NF‐E2 is essential for establishment of a tissue‐specific histone modification pattern, J. Biol. Chem., 279: 7456–7461, 2004. [DOI] [PubMed] [Google Scholar]
  • 25. Armstrong J.A., Emerson B.M., NF‐E2 disrupts chromatin structure at human β‐globin locus control region hypersensitive site 2 in vitro , Mol. Cell. Biol., 16: 5634–5644, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Turner J, Crossley M., Basic Krüppel‐like factor function within a network of interacting haematopoietic transcription factors, Int. J. Biochem. Cell. Biol., 31: 1169–1174, 1999. [DOI] [PubMed] [Google Scholar]
  • 27. Perkins A., Erythroid Krüppel like factor: from fishing expedition to gourmet meal, Int J. Biochem. Cell. Biol., 31: 1175–1192, 1999. [DOI] [PubMed] [Google Scholar]
  • 28. Donze D, Townes T.M., Bieker J.J., Role of erythroid Krüppel‐like factor in human gamma‐ to beta‐globin gene switching, J. Biol. Chem., 270: 1955–1959, 1995. [DOI] [PubMed] [Google Scholar]
  • 29. Zhang W.J., Kadam S., Emerson B.M., Bieker J.J., Site‐specific acetylation by p300 or CREB binding protein regulates erythroid Krüppel‐like factor transcriptional activity via its interaction with the SWI‐SNF complex, Mol. Cell. Biol., 21: 2413–2422, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Zhang W, Bieker J.J., Acetylation and modulation of erythroid Krüppel‐like factor (EKLF) activity by interaction with histone acetyltransferases, Proc. Natl. Acad. Sci. USA., 95: 9850–9860, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. Chen X.Y., Bieker J.J., Unanticipated repression function linked to erythroid Krüppel‐like factor, Mol. Cel. Biol., 21: 3118–3125, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Dorfman D.M., Wilson D.B., Bruns G.A.P., Orkin S.H., Human transcription factor GATA‐2; evidence for regulation of preproendothelin‐1 gene expression in endothelia cells, J. Biol. Chem., 267: 1279–85, 1992. [PubMed] [Google Scholar]
  • 33. Nagai T., Harigae H., Ishihara H., Motohashi H., Minegishi N., Tsuchiya S., Hayashi N., Gu L., Andres B., and Engel J.D., Transcription factor GATA‐2 is expressed in erythroid, early myeloid and CD34+ human leukemia‐derived cell lines, Blood, 84: 1074–84, 1994. [PubMed] [Google Scholar]
  • 34. Briegel K., Lim K.C., Plank C., Beug H., Engel J.D., Zenke M., Ectopic expression of a conditional GATA‐2/estrogen receptor chimera arrests erythroid differentiation in a hormone‐dependent manner, Genes. Dev., 7: 1097–109, 1993. [DOI] [PubMed] [Google Scholar]
  • 35. Hayakawa F, Towatari M, Ozawa Y, Tomita A, Privalsky ML, Saito H., Functional regulation of GATA‐2 by acetylation, J. Leukoc. Biol., 75: 529–40, 2004. [DOI] [PubMed] [Google Scholar]
  • 36. Grass J.A., Boyer M.E., Pal S., Grass J.A., Boyer M.E., Pal S., Wu J., Weiss M.J., Bresnick E.H., GATA‐1‐dependent transcriptional repression of GATA‐2 via disruption of positive autoregulation and domain‐wide chromatin remodeling, Proc. Natl. Acad. Sci. U S A., 100: 8811–6, 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. Ozawa Y., Towatari M., Tsuzuki S., Hayakawa F., Maeda T., Miyata Y., Tanimoto M, Saito H., Histone deacetylase 3 associates with and represses the transcription factor GATA‐2, Blood, 98: 2116–2123, 2001. [DOI] [PubMed] [Google Scholar]
  • 38. Hershfield M.S., Kurtzberg J., Harden E., Moore J.O., Whang‐Peng Je., and Haynes BF., Conversion of a stem cell leukemia from a T‐lymphoid to a myeloid phenotype induced by the adenosine deaminase inhibitor 2′‐deoxycoformycin, Proc. Natl. Acad. Sci. USA., 81: 253–257, 1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. Begley C.G., Visvader J., Green A.R., Aplan P.D., Metcalf D., and Gough N.M., Molecular cloning and chromosomal localization of the murine homology of the human helix‐loop‐helix gene SCL, Proc. Natl. Acad. Sci. USA., 88: 869–873, 1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40. Shivdasani R.A., Orkin S.H., The transcriptional control of hematopoiesis, Blood, 87: 4025–4039, 1996. [PubMed] [Google Scholar]
  • 41. Wadman I.A., Osada H., Grutz G.G., Agulnick A.D., Westphal H., Forster A., Rabbitts T.H., The LIM‐only protein Lmo2 is a bridging molecular assembling an erythroid, DNA‐binding complex which includes the TAL1, E47, GATA‐1 and Ldb1/NLI proteins, EMBO. J., 16: 3145–3157, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42. Aplan P.D., Nakahara K., Orkin S.H., Kirsch IR., The SCL gene product: a positive regulator of erythroid differentiation, EMBO. J., 11: 4073–81, 1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. Huang S., Qiu Y., Stein R.W., Brandt S.J., p300 functions as a transcriptional coactivator for the TAL1/SCL oncoprotein, Oncogene, 18: 4958–4967, 1999. [DOI] [PubMed] [Google Scholar]
  • 44. Huang S., Qiu Y., Shi Y., Xu Z., Brandt S.J., P/CAF ‐ mediated acetylation regulates the function of the basic helix‐loop‐helix transcription factor TAL1/SCL, EMBO. J., 19: 6792–6803, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45. Huang S., Brandt S.J., mSin3A regulates murine erythroleukemia cell differentiation through association with the TAL (or SCL) transcription factor, Mol. Cell. Biol., 20: 2248–2259, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. O'Neil J., Shank J., Cusson N., Murre C., Kelliher M., TAL1/SCL induces leukemia by inhibiting the transcriptional activity of E47/HEB, Cancer Cell, 5: 587–596, 2004. [DOI] [PubMed] [Google Scholar]
  • 47. Shivdasani R.A., Orkin S.H., The transcriptional control of hematopoiesis, Blood, 87: 4025–4039, 1996. [PubMed] [Google Scholar]
  • 48. Sakura, H , Kanei‐Ishii, C , Nagase, T , Nakagoshi H, Gonda T.J., Ishii S., Delineation of three functional domains of the transcriptional activator encoded by the c‐myb protonocogene, Proc. Natl. Acad. Sci. USA., 86: 5758–576, 1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49. Sano Y.J. Ishii S., Increased affinity of c‐myb for CREB‐binding protein (CBP) after CBP‐induced acetylation, J. Biol. Chem., 276: 3674–3682, 2001. [DOI] [PubMed] [Google Scholar]
  • 50. Tomita A., Towatari M., Tsuzuki S., Hayakawa F., Kosugi H., Tamai K., Miyazaki T., Kinoshita T., Saito H., c‐Myb acetylation at the carboxyl‐terminal conserved domain by transcriptional co‐activator p300, Oncogene, 19: 444–451, 2000. [DOI] [PubMed] [Google Scholar]
  • 51. Gerd A., Blobel G.A., CREB‐binding protein and p300: molecular integrators of hematopoietic transcription, Blood, 95: 745–755, 2000. [PubMed] [Google Scholar]
  • 52. Scott E.W., Simon M.C., Anastasi J., Singh H., Recruitment of transcription factor PU.1 in the development of multiple hematopoietic lineages, Science, 265: 1573–1577, 1994. [DOI] [PubMed] [Google Scholar]
  • 53. Ben‐David, Y. , Bernstein, A. , Friend virus‐induced erythroleukemia and nultistage nature of cancer, Cell, 66: 831–834, 1991. [DOI] [PubMed] [Google Scholar]
  • 54. Hong W., Kim A.Y., Ky S., Rakowski C., Seo S.‐B., Chakravarti D., Atchison M., Blobel G.A., Inhibition of CBP‐mediated protein acetylation by the Ets family oncoprotein PU.1, Mol. Cell. Biol., 11: 3729–3743, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55. Laribee R.N. Klemsz M.J., Loss of PU.1 expression following inhibition of histone deacetylation, J. Immun., 167: 5160–5166, 2001. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES