STEROID-RECEPTOR COACTIVATOR-1 IS A HISTONE ACETYLTRANSFERASE

Steroid receptors and coactivator proteins are thought to stimulate ge ne expression by facilitating the assembly of basal transcription fact ors into a stable preinitiation complex(1). That is not clear, however , is how these transcription factors gain access to transcriptionally repressed chromatin to modulate the transactivation of specific gene n etworks in vitro. The available evidence indicates that acetylation of chromatin in vivo is coupled to transcription and that specific histo ne acetyltransferases (HATs) target histones bound to DNA and overcome the inhibitory effect of chromatin on gene expression(2-4). The stero id-receptor coactivator SRC-1 is a coactivator for many members of the steroid-hormone receptor superfamily of Ligand-inducible transcriptio n factors(5), Here we show that SRC-1 possesses intrinsic histone acet yltransferase activity and that it also interacts with another HAT, p3 00/CBP-associate factor (PCAF). The HAT activity of SRC-1 maps to its carboxy-terminal region and is primarily specific for histones H3 and H4, Acetylation by SRC-1 and PCAF of histones bound at specific promot ers may result from ligand binding to steroid receptors and could be a mechanism by which the activation functions of steroid receptors and associated coactivators enhance formation of a stable preinitiation co mplex, thereby increasing transcription of specific genes from transcr iptionally repressed chromatin templates.