What's Up and Down with Histone Deacetylation and Transcription?

Chromatin structure is an important component of gene expression, and recent developments have led to increased interest in the role of core histone acetylation in transcriptional regulation. It has been recognized for many years that there is a general correlation between core histone acetylation and gene activity, and the notion that core histone acetylation facilitates gene expression has gained further support as transcription factors such as Gcn5, CBP /p300, and TAF sub(11)250 have been found to possess histone acetyl-transferase activity. Conversely, it has been thought that core histone deacetylation leads to transcriptional repression. This hypothesis was found to be partly consistent with the observation that a mammalian histone deacetylase, HDAC1 (also known as HD1), is related to the yeast Rpd3 protein, which is required for full repression as well as full activation of gene expression. In addition, another mammalian protein, termed HDAC2 (also known as mRPD3), was identified as a YY1-binding protein (YY1 is a sequence-specific DNA-binding protein that can act as a repressor or activator), and a Gal4-HDAC2 fusion protein was found to repress transcription in a transient transfection assay. In this context, we will summarize recent findings in the study of histone deacetylases, and then discuss a few speculative models by which protein acetylation might affect gene activity.