2l75
Solution structure of CHD4-PHD2 in complex with H3K9me3
Structural highlights
FunctionCHD4_HUMAN Component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin by deacetylating histones.[1] [2] Publication Abstract from PubMedA major challenge in chromatin biology is to understand the mechanisms by which chromatin is remodelled into active or inactive states as required during development and cell differentiation. One complex implicated in these processes is the Nucleosome Remodelling and histone Deacetylase (NuRD) complex, which contains both histone deacetylase and nucleosome remodelling activities and has been implicated in the silencing of subsets of genes involved in various stages of cellular development. Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a core component of the NuRD complex, and contains a nucleosome remodelling ATPase domain along with two chromodomains and two plant homeodomain (PHD) fingers. We have previously demonstrated that the second PHD finger of CHD4 binds peptides corresponding to the N-terminus of histone H3 methylated at K9. Here, we determine the solution structure of PHD2 in complex with H3K9me3, revealing the molecular basis of histone recognition including a cation-pi recognition mechanism for methylated K9. Additionally we demonstrate that the first PHD finger also exhibits binding to the N-terminus of H3, and we establish the histone-binding surface of this domain. This is the first instance where a histone-binding ability has been demonstrated for two separate PHD modules within the one protein. These findings suggest that CHD4 could bind to two H3 N-terminal tails on the same nucleosome or on two separate nucleosomes simultaneously, presenting exciting implications for the mechanism by which CHD4 and the NuRD complex could direct chromatin remodelling. The plant homeodomain (PHD) fingers of CHD4 are histone H3-binding modules with preference for unmodified H3K4 and methylated H3K9.,Mansfield RE, Musselman CA, Kwan AH, Garske AL, Davrazou F, Denu JM, Kutateladze TG, Mackay JP J Biol Chem. 2011 Jan 28. PMID:21278251[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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