Physiological roles of class I HDAC complex and histone demethylase

Abstract

Epigenetic gene silencing is one of the fundamental mechanisms for ensuring proper gene expression patterns during cellular differentiation and development. Histone deacetylases (HDACs) are evolutionally conserved enzymes that remove acetyl modifications from histones and play a central role in epigenetic gene silencing. In cells, HDAC forms a multiprotein complex (HDAC complex) in which the associated proteins are believed to help HDAC carry out its cellular functions. Though each HDAC complex contains distinct components, the presence of isoforms for some of the components expands the variety of complexes and the diversity of their cellular roles. Recent studies have also revealed a functional link between HDAC complexes and specific histone demethylases. In this paper, we summarize the distinct and cooperative roles of four class I HDAC complexes, Sin3, NuRD, CoREST, and NCoR/SMRT, with respect to their component diversity and their relationship with specific histone demethylases.

Figure 1

The Sin3 complexes. Schematic representation of the Sin3-containing HDAC complexes: (a) the Sin3-core and Sin3-RBP2 complexes in mammalian cells; (b) the Rpd3S complex in S. cerevisiae; (c) RLAF-N and LAF-A complexes in Drosophila. The empty dotted boxes indicate missing subunits compared with the Sin3-core complex.

Figure 2

The NuRD complexes. Schematic representation of the NuRD complex (a) and ES cell-specific NODE complex (b). The empty dotted boxes indicate missing subunits compared with the NuRD complex.

Figure 3

The CoREST and NCoR/SMRT complexes. Schematic representation of the CoREST (a) and the NCoR/SMRT (b) complexes. The CoREST complex is included in the CtBP-containing complexes. The empty dotted boxes indicate that both CoREST and NCoR/SMRT complexes lack RbAp46/RbAp48 subunits, which are widely observed in HDAC-containing complexes.