CoREST is an integral component of the CoREST- human histone deacetylase complex

Abstract

Here we describe the components of a histone deacetylase (HDAC) complex that we term the CoREST-HDAC complex. CoREST-HDAC is composed of polypeptides distinct from previously characterized HDAC1/2-containing complexes such as the mSin3 and nucleosome remodeling and deacetylating (NRD, also named NURD, NuRD) complex. Interestingly, we do not observe RbAp46 and RbAp48 in this complex, although these proteins have been observed in all previously identified complexes and are thought to be part of an HDAC1/2 core. We identify the transcriptional corepressor CoREST and a protein with homology to polyamine oxidases as components of CoREST-HDAC. The HDAC1/2-interacting region of CoREST is mapped to a 179-aa region containing a SANT domain, a domain found in other HDAC1/2-interacting proteins such as NCoR, MTA1, and MTA2. Furthermore, we demonstrate that the corepressor function of CoREST depends on this region. Although CoREST initially was cloned as a corepressor to REST (RE1 silencing transcription factor/neural restrictive silencing factor), we find no evidence for the existence of the eight-zinc finger REST transcription factor as an interacting partner in this complex; however, we do find evidence for association of the putative oncogene ZNF 217 that contains eight zinc fingers.