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 hematopoletic 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. (C) 2001 by The American Society of Hematology