We have previously demonstrated that high concentrations of glucose stimulate insulin gene expression by causing hyperacetylation of histone H4 at the insulin gene promoter. Furthermore, we have shown that the glucose-mediated hyperacetylation of histone H4 depends on the recruitment of the histone acetyltransferase p300 by the beta cell-specific transcription factor Pdx-1. In this study, we de...

Histone deacetylases (HDACs) catalyze the deacetylation of lysine residues on histones and non-histone proteins. HDACs have been shown to control the functions of key cell cycle proteins. Consistent with this, the overexpression of HDACs has been observed in multiple cancers, resulting in deregulation of the cell cycle and uncontrolled proliferation. This review focuses on the impact that HDACs...

Yeast contains a family of five related histone deacetylases (HDACs) whose functions are known at few genes. Therefore, we used chromatin immunoprecipitation and intergenic microarrays to generate genome-wide HDAC enzyme activity maps. Rpd3 and Hda1 deacetylate mainly distinct promoters and gene classes where they are recruited largely by novel mechanisms. Hda1 also deacetylates subtelomeric do...

In eukaryotes, duplication of genomic information depends on the sequential activation of multiple replication origins distributed along the chromosomes. Replication origins differ in initiation time, chromatin structure and three-dimensional position in the nucleus. Recently, we have performed a systematic analysis of the role of histone deacetylases (HDACs) in the regulation of origin activit...

The class I histone deacetylases (HDACs) HDAC1 and HDAC2 play partially redundant roles in the regulation of gene expression and mouse development. As part of multisubunit corepressor complexes, these two deacetylases exhibit both enzymatic and nonenzymatic functions. To examine the impact of the catalytic activities of HDAC1 and HDAC2, we generated knock-in mice expressing catalytically inacti...