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.
Hayakawa
Fumihiko
F
First Department of Internal Medicine, Nagoya University School of Medicine, Japan. fhayakawa@ucdavis.edu
Towatari
Masayuki
M
Ozawa
Yukiyasu
Y
Tomita
Akihiro
A
Privalsky
Martin L
ML
Saito
Hidehiko
H
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050989:GATA2 Transcription Factor; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000378:metabolism; D051548:Histone Acetyltransferases; D006801:Humans; D009154:Mutation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; D051548:Histone Acetyltransferases; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C494711:GATA2 protein, human; C501179:KAT2A protein, human