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Functional regulation of GATA‐2 by acetylation
Author(s) -
Hayakawa Fumihiko,
Towatari Masayuki,
Ozawa Yukiyasu,
Tomita Akihiro,
Privalsky Martin L.,
Saito Hidehiko
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0603389
Subject(s) - acetylation , biology , gata2 , haematopoiesis , zinc finger , transcription factor , progenitor cell , transfection , microbiology and biotechnology , in vitro , gata transcription factor , stem cell , cell culture , promoter , gene , genetics , gene expression
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.