Functional regulation of GATA‐2 by acetylation

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.

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