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Published online before print December 12, 2003

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0603389

Received for publication June 24, 2003.
Revised November 7, 2003.
Accepted for publication November 18, 2003.

Article

Functional regulation of GATA-2 by acetylation

Fumihiko Hayakawa ^*@, Masayuki Towatari ^*, Yukiyasu Ozawa ^*, Akihiro Tomita ^*, Martin L. Privalsky , and Hidehiko Saito ^*

*First Department of Internal Medicine, Nagoya University School of Medicine, Japan; and Section of Microbiology, Division of Biological Sciences, University of California at Davis

^@ To whom correspondence should be addressed. E-mail: fhayakawa{at}ucdavis.edu.

	Abstract

The transcription factor GATA-2 is expressed in hematopoietic stem and progenitor cells and is functionally implicated in their survival and proliferation. In the present study, we show that GATA-2 exists as an acetylated protein in immature precursor cells, KG1. GATA-2 was acetylated in vitro by p300 and GCN5. We have identified multiple acetylation sites by p300 on GATA-2, which include sites outside the zinc finger domain. We confirmed that GATA-2 acetylation occurred in transiently transfected 293T cells at sites similar to those induced by p300 in vitro. We have successfully shown that acetylation of GATA-2 in vitro increased its DNA-binding activity. In addition, GATA-2 displayed a transcriptional synergism with p300 that was impaired by mutation of each acetylation site. More importantly, each mutation in the acetylation sites of GATA-2 abolished its growth inhibitory effect on an interleukin-3-dependent progenitor, 32D. We conclude that acetylation provides multiple control points for the regulation of GATA-2 function.

Key Words: p300 • GCN5 • histone acetyl transferase • transcription factor • DNA-binding activity

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