CHROMATIN DEACETYLATION BY AN ATP-DEPENDENT NUCLEOSOME REMODELING COMPLEX

The dynamic assembly and remodelling of eukaryotic chromosomes facilit ate fundamental cellular processes such as DNA replication and gene tr anscription. The repeating unit of eukaryotic chromosomes is the nucle osome fore, consisting of DNA wound about a defined octamer of histone proteins(1). Two enzymatic processes that regulate transcription by t argeting elements of the nucleosome include ATP-dependent nucleosome r emodelling and reversible histone acetylation(2,3). The histone deacet ylases, however, are unable to deacetylate oligonucleosomal histones i n vitro(4). The protein complexes that mediate ATP-dependent nucleosom e remodelling and histone acetylation/deacetylation in the regulation of transcription were considered to be different, although it has rece ntly been suggested that these activities might be coupled(5). We repo rt here the identification and functional characterization of a novel ATP-dependent nucleosome remodelling activity that is part of an endog enous human histone deacetylase complex This activity is derived from the CHD3 and CHD4 proteins which contain helicase/ATPase domains found in SWI2-related chromatin remodelling factors, and facilitates the de acetylation of oligonucleosomal histones in vitro. We refer to this co mplex as the nucleosome remodelling and deacetylating (NRD) complex. O ur results establish a physical and functional link between the distin ct chromatin-modifying activities of histone deacetylases and nucleoso me remodelling proteins.