Histone H4 HDAC activity is necessary for expression of the PU.1 gene.

Although the current paradigm delegates histone deacetylases (HDACs) to the role of transcriptional co-repressors, we recently showed that HDAC activity was necessary for expression of the hematopoietic transcription factor PU.1. Chromatin immunoprecipitation analyses showed that inhibition of HDACs resulted in increased histone H4 acetylation within the promoter and intron 1 regions of the PU.1 locus. In contrast, increases in both H3 and H4 acetylation were seen for introns 2, 3 and 4 on the 3' end of the PU.1 locus. Maximal increases in histone H4 acetylation over the promoter and intron 1 region were seen within 10 min of HDAC inhibition, while the increases seen on the 3' end showed slower kinetics. The increases in H4 acetylation were reversible and decreased levels of acetylation correlated with re-expression of the PU.1 gene. Finally, we show that HDAC activity is required for association of RNA polymerase II with the PU.1 promoter.