Histone deacetylase 3 associates with and represses the transcription factor GATA-2.
The zinc finger transcription factor GATA-2 plays a critical role in the survival and proliferation of hematopoietic stem cells. This study examined the interaction of GATA-2 with histone deacetylases (HDACs) to define the involvement of HDACs in the regulation of GATA-2 function. GATA-2 directly associates with HDAC3 but not with HDAC1. Consistent with this, HDAC3 suppressed the transcriptional potential of GATA-2, whereas HDAC1 did not affect GATA-2-dependent transcription. Results further demonstrated that GATA-2 and HDAC3 colocalized in the nucleus. These results identify GATA-2 as a nuclear target for HDAC3-mediated repression. Furthermore, GATA-2 also directly associated with HDAC5 but not with other class II HDACs examined, that is, HDAC4 and HDAC6. This is the first demonstration that a tissue-specific transcription factor directly and selectively interacts with HDAC3 and HDAC5 among HDAC family members.
Ozawa
Y
Y
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan.
Towatari
M
M
Tsuzuki
S
S
Hayakawa
F
F
Maeda
T
T
Miyata
Y
Y
Tanimoto
M
M
Saito
H
H
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050989:GATA2 Transcription Factor; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D011485:Protein Binding; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014162:Transfection; D016335:Zinc Fingers; D000099186:Histone Deacetylase 3
D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; D006655:Histone Deacetylases; D014157:Transcription Factors; D000099186:Histone Deacetylase 3; C494711:GATA2 protein, human