Functional regulation of GATA-2 by acetylation

The transcription factor GATA-2 is ex- pressed 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 imma- ture 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 suc- cessfully 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 acet- ylation site. More importantly, each mutation in the acetylation sites of GATA-2 abolished its growth inhibitory effect on an interleukin-3-depen- dent progenitor, 32D. We conclude that acetyla- tion provides multiple control points for the regu- lation of GATA-2 function. J. Leukoc. Biol. 75: 000-000; 2004.