Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

c-Myb acetylation at the carboxyl-terminal conserved domain by transcriptional co-activator p300

Abstract

Transcription factor c-Myb plays important roles in cell survival and differentiation in immature hematopoietic cells. Here we demonstrate that c-Myb is acetylated at the carboxyl-terminal conserved domain by histone acetyltransferase p300 both in vitro and in vivo. The acetylation sites in vivo have been located at the lysine residues of the conserved domain (K471, K480, K485) by the use of the mutant Myb (Myb-KAmut), in which all three lysine residues are substituted into alanine. Electrophoretic mobility shift assay reveals that Myb-KAmut shows higher DNA binding activity than wild type c-Myb and that acetylation of c-Myb in vitro by p300 causes dramatic increase in DNA binding activity. Accordingly, transactivation activity of both mim-1 and CD34 promoters by Myb-KAmut is higher than that driven by wild type c-Myb. Furthermore, the bromodomain of p300, in addition to the histone acetyltransferase (HAT) domain, is required for effective acetylation of c-Myb, and hGCN5 is revealed to be a factor acetyltransferase for c-Myb in vitro. We present a new manner of post-translational modification of the c-Myb protein and the potential significance of the acetylation in c-Myb.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Aziz N, Miglarese MR, Hendrickson RC, Shabanowitz J, Sturgill TW, Hunt DF and Bender TP. . 1995 Proc. Natl. Acad. Sci. USA 92: 6429–6433.

  • Bannister AJ and Kouzarides T. . 1996 Nature 384: 641–643.

  • Bies J and Wolff L. . 1997 Oncogene 16: 203–212.

  • Boyes J, Byfield P, Nakatani Y and Ogryzko V. . 1998 Nature 396: 594–598.

  • Burn TC, Satterthwaite AB and Tenen DG. . 1992 Blood 80: 3051–3059.

  • Dai P, Akimaru H, Tanaka Y, Hou DX, Yasukawa T, Kanei-Ishii C, Takahashi T and Ishii S. . 1996 Genes Dev. 10: 528–540.

  • Dash AB, Orrico FC and Ness SA. . 1996 Genes Dev. 10: 1858–1869.

  • Dhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK and Zhou MM. . 1999 Nature 399: 491–496.

  • Dubendorff JW, Whittaker LJ, Eltman JT and Lipsick JS. . 1992 Genes Dev. 6: 2524–2535.

  • Gonda TJ and Bishop JM. . 1983 J. Virol. 46: 212–220.

  • Gonda TJ. . 1998 Int. J. Biochem. Cell Biol. 30: 547–551.

  • Grasser FA, Graf T and Lipsick JS. . 1991 Mol. Cell. Biol. 11: 3987–3996.

  • Gu W and Roeder RG. . 1997 Cell 90: 595–606.

  • Guehmann S, Vorbrueggen G, Kalkbrenner F and Moelling K. . 1992 Nucleic Acids Res. 20: 2279–2286.

  • Hu YL, Ramsay RG, Kanei-Ishii C, Ishii S and Gonda TJ. . 1991 Oncogene 6: 1549–1553.

  • Hung HL, Lau J, Kim AY, Weiss MJ and Blobel GA. . 1999 Mol. Cell Biol. 19: 3496–3505.

  • Imhof A, Yang XJ, Ogryzko VV, Nakatani Y, Wolffe AP and Ge H. . 1997 Curr. Biol. 7: 689–692.

  • Introna M, Luchetti M, Castellano M, Arsura M and Golay J. . 1994 Semin. Cancer Biol. 5: 113–124.

  • Kanei-Ishii C, MacMillan EM, Nomura T, Sarai A, Ramsay RG, Aimoto S, Ishii S and Gonda TJ. . 1992 Proc. Natl. Acad. Sci. USA 89: 3088–3092.

  • Klempnauer KH, Gonda TJ and Bishop JM. . 1982 Cell 31: 453–463.

  • Kuo MH, Brownell JE, Sobel RE, Ranalli TA, Cook RG, Edmondson DG, Roth SY and Allis CD. . 1996 Nature 383: 269–272.

  • Lipsick JS and Wang D. . 1999 Oncogene 18: 3047–3055.

  • Liu L, Scolnick DM, Trievel RC, Zhang HB, Marmorstein R, Halazonetis TD and Berger SL. . 1999 Mol. Cell Biol. 19: 1202–1209.

  • Melotti P, Ku DH and Calabretta B. . 1994 J. Exp. Med. 179: 1023–1028.

  • Miglarese MR, Richardson AF, Azis N and Bender TP. . 1996 J. Biol. Chem. 271: 22697–22705.

  • Mucenski ML, McLain K, Kier AB, Swerdlow SH, Schreiner CM, Miller TA, Pietryga DW, Scott Jr WJ and Potter SS. . 1991 Cell 65: 677–689.

  • Nakahara Y, Suzuki H, Ohashi H, Hatano S, Tomita A, Kinoshita T, Murate T, Saito H and Hotta T. . 1999 Int. J. Hematol. 69: 237–243.

  • Ness SA, Marknell A and Graf T. . 1989 Cell 59: 1115–1125.

  • Ness SA. . 1999 Oncogene 18: 3039–3046.

  • Nomura N, Takahashi M, Matsui M, Ishii S, Date T, Sasamoto S and Ishizaki R. . 1988 Nucleic Acids Res. 16: 11075–11089.

  • Ogryzko VV, Schiltz RL, Russanova V, Howard BH and Nakatani Y. . 1996 Cell 87: 953–959.

  • Oh I and Reddy EP. . 1999 Oncogene 18: 3017–3033.

  • Sakaguchi K, Herrera JE, Saito S, Miki T, Bustin M, Vassilev A, Anderson CW and Appella E. . 1998 Genes Dev. 12: 2831–2841.

  • Sakura H, Kanei-Ishii C, Nagase T, Nakagoshi H, Gonda TJ and Ishii S. . 1989 Proc. Natl. Acad. Sci. USA 86: 5758–5762.

  • Struhl K. . 1998 Genes Dev. 12: 599–606.

  • Tanaka Y, Nomura T and Ishii S. . 1997 FEBS Lett. 413: 162–168.

  • Tashiro S, Takemoto Y, Handa H and Ishii S. . 1995 Oncogene 10: 1699–1707.

  • Tomita A, Watanabe T, Kosugi H, Ohashi H, Uchida T, Kinoshita T, Mizutani S, Hotta T, Murate T, Seto M and Saito H. . 1998 Leukemia 12: 1422–1429.

  • Vorbrueggen G, Kalkbrenner F, Guehmann S and Moelling K. . 1994 Nucleic Acids Res. 22: 2466–2475.

  • Waltzer L and Bienz M. . 1998 Nature 395: 521–525.

  • Wang L, Mizzen C, Ying C, Candau R, Barlev N, Brownell J, Allis CD and Berger SL. . 1997 Mol. Cell. Biol. 17: 519–527.

  • Weston K. . 1999 Oncogene 18: 3034–3038.

  • Xu W, Edmundson DG and Roth SY. . 1998 Mol. Cell. Biol. 18: 5659–5669.

  • Zhang W and Bieker JJ. . 1998 Proc. Natl Acad. Sci. USA 95: 9855–9860.

Download references

Acknowledgements

We thank SA Ness and A Fukamizu for providing reagents, H Ohashi for critical reading, H Iida, S Hatano and K Kondo for technical assistance.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tomita, A., Towatari, M., Tsuzuki, S. et al. c-Myb acetylation at the carboxyl-terminal conserved domain by transcriptional co-activator p300. Oncogene 19, 444–451 (2000). https://doi.org/10.1038/sj.onc.1203329

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203329

Keywords

This article is cited by

Search

Quick links