CHD 4 is a dynamic component of the NuRD complex 1 CHD 4 is a Peripheral Component of the Nucleosome Remodeling and Deacetylase Complex

Chromatin remodeling enzymes act to dynamically regulate gene accessibility. In many cases, these enzymes function as large multicomponent complexes that, in general, comprise a central ATP-dependent Snf2-family helicase that is decorated with a variable number of regulatory subunits. The Nucleosome Remodeling and Deacetylase complex (NuRD), which is essential for normal development in higher organisms, is one such macromolecular machine. The NuRD complex comprises approximately 10 subunits, including the histone deacetylases 1 and 2 (HDAC1 and HDAC2), and is defined by the presence of a CHD-family remodeling enzyme – most commonly Chromodomain Helicase DNAbinding protein 4 (CHD4). The existing paradigm holds that CHD4 acts as the central hub upon which the complex is built. We show here that this paradigm does not, in fact, hold and that CHD4 is only a peripheral and dynamic component of the NuRD complex. A complex lacking CHD4 that has HDAC activity can exist as a stable species in cells. The addition of recombinant CHD4 to this Nucleosome Deacetylase (NuDe) complex reconstitutes a NuRD complex with nucleosome remodeling activity. These data are an important step towards understanding the architecture of the NuRD complex. Nucleosomes effectively act as a roadblock to all aspects of genome biology. ATPdependent chromatin remodeling enzymes solve this problem by using ATP-derived energy to alter the positions, occupancy and composition of nucleosomes. All remodelers possess a highlyrelated ATPase motor domain from the helicase family and are classified into four subfamilies (INO80, ISWI, SWR1 and CHD) based on sequence similarity (1). Each subfamily is represented in nearly all eukaryotes, suggesting that they catalyse different remodeling events. For example, ISWI proteins reposition (or slide) nucleosomes to create regularly spaced arrays; this periodic organisation is a key characteristic of DNA at the start of genes (2). SWR1 and INO80 enzymes have opposing roles in histone variant dynamics; the former incorporates these histone variants (e.g., H2A.Z) while the latter removes them. These variants set up specific chromatin structures that modulate transcription and replication, although the roles of many variants are http://www.jbc.org/cgi/doi/10.1074/jbc.M115.707018 The latest version is at JBC Papers in Press. Published on May 27, 2016 as Manuscript M115.707018 Copyright 2016 by The American Society for Biochemistry and Molecular Biology, Inc. by gest on M ay 1, 2016 hp://w w w .jb.org/ D ow nladed from CHD4 is a dynamic component of the NuRD complex