In the intact cell, DNA closely associates with histones and other nuclear
proteins to form chromatin. The remodeling of chromatin is believed to be
a critical component of transcriptional regulation and a major source of this
remodeling is brought about by the acetylation of nucleosomal histones. Acetylation
of lysine residues in the amino-terminal tail domain of histone results
in an allosteric change in the nucleosomal conformation and an increased
accessibility to transcription factors by DNA. Conversely, the deacetylation
of histones is associated with transcriptional silencing. Several mammalian
proteins have been identified as nuclear histone acetylases, including GCN5,
PCAF (for p300/CBP-associated factor), p300/CBP and the TFIID subunit TAF
II p250. Mammalian HDAC1 (also designated HD1), HDAC2 (also designated
mammalian RPD3) and HDAC3, all of which are related to the yeast transcriptional
regulator Rpd3p, have been identified as histone deacetylases.