Long-range effects of histone point mutations on DNA remodeling revealed from computational analyses of SIN-mutant nucleosome structures.

Nucleic Acids Research
Fei XuWilma K Olson

Abstract

The packaging of DNA into nucleosomes impedes the binding and access of molecules involved in its processing. The SWI/SNF multi-protein assembly, found in yeast, is one of many regulatory factors that stimulate the remodeling of DNA required for its transcription. Amino-acid point mutations in histones H3 or H4 partially bypass the requirement of the SWI/SNF complex in this system. The mechanisms underlying the observed remodeling, however, are difficult to discern from the crystal structures of nucleosomes bearing these so-called SIN (SWI/SNF INdependent) mutations. Here, we report detailed analyses of the conformations and interactions of the histones and DNA in these assemblies. We find that the loss of direct protein-DNA contacts near point-mutation sites, reported previously, is coupled to unexpected additional long-range effects, i.e. loss of intermolecular contacts and accompanying DNA conformational changes at sequentially and spatially distant sites. The SIN mutations seemingly transmit information relevant to DNA binding across the nucleosome. The energetic cost of deforming the DNA to the states found in the SIN-mutant structures helps to distinguish the mutants that show phenotypes in yeast from those that do not. M...Continue Reading

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Citations

Oct 29, 2013·The Journal of Chemical Physics·Mandar Kulkarni, Arnab Mukherjee
Nov 13, 2012·Cell·Lacramioara BintuCarlos Bustamante
Jan 8, 2015·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Sam Meyer, Ralf Everaers

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Datasets Mentioned

BETA
GM20861
GM34809

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BETA
X-ray

Software Mentioned

3DNA

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