Biology

Dr. Kalyan Sinha
Department of Biochemistry and Biophysics, University of California, San Francisco

Abstract:

Mobilization of nucleosomal DNA by ATP-dependent chromatin remodeling enzymes plays essential biological roles by regulating the access of DNA to gene expression machinery. Hitherto, the mechanism by which nucleosomal DNA is mobilized despite of the steric constraints placed by the histone octamer remains unknown. In this work, using methyl transverse-relaxation-optimized NMR spectroscopy (TROSY) on a 450 kDa complex of a nucleosome bound to an ISWI chromatin remodeler, SNF2h, it has been shown that the remodeler distorts the histone octamer. Binding of SNF2h in an activated ATP state changes dynamics of buried histone residues. Preventing octamer distortion by site-specific disulfide linkages inhibits nucleosome sliding by SNF2h, while promoting octamer eviction by the SWI/SNF complex, RSC. These findings reveal that the histone core of a nucleosome is more plastic than previously imagined, and that octamer deformation plays different roles based on the type of chromatin remodeler. The observed plasticity of nucleosome core is likely to have general consequences for events related to chromatin regulation beyond ATP-dependent remodeling.