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

RbAp48 (RbAp46 and RbAp48 are closely related proteins). Perhaps significantly, RbAp48 is associated with Department of Biology and Center for Molecular Genetics HDAC1 (Taunton et al., 1996) and is also a subunit of chromatin assembly factor 1 (for reviews, see Roth and A brief guide to the factors that were studied in each of the papers is given in Table 1. Chromatin structure is an important component of gene What do these seven papers say? Do they have a expression, and recent developments have led to in-common message? The major point of these papers is creased interest in the role of core histone acetylation that transcriptional repression by a sequence-specific in transcriptional regulation (for reviews, see Roth and DNA-binding factor can be mediated by the recruitment It of a deacetylase (Rpd3/HDAC1/HDAC2) to the promoter has been recognized for many years that there is a gen-region. More specifically, each of the papers proposes eral correlation between core histone acetylation and a chromatin-specific mechanism for repression by a se-gene activity, and the notion that core histone acetyla-quence-specific DNA-binding protein that involves tion facilitates gene expression has gained further sup-deacetylation of core histones by a histone deacetylase port as transcription factors such as Gcn5, CBP/p300, that is linked to the DNA-bound repressor via Sin3 and/ and TAF II 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; Taunton et al., 1996), is related to the yeast Rpd3 protein, which is required for full repression as well as full activation of gene expression (Vidal and Gaber, 1991). In addition, another mam-malian 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 (Yang et al., 1996). 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 Figure 1. A Summary of Proposed Interactions That Occur between might affect gene activity. Recent findings suggest the following generalized model for tran-scriptional repression by DNA-binding repressors that can interact Seven new and interesting papers (Alland et …