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Structural Studies of ATP‐dependent chromatin remodeling
Author(s) -
Leschziner Andres,
Isaac Berith,
Clapier Cedric R,
Cairns Bradley R
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.832.1
Subject(s) - nucleosome , chromatin structure remodeling (rsc) complex , chromatin , chromatin remodeling , histone , atp hydrolysis , acetylation , protein subunit , aaa proteins , microbiology and biotechnology , atpase , biophysics , dna , biology , chemistry , biochemistry , gene , enzyme
ATP‐dependent chromatin remodeling complexes (“remodelers”) are large macromolecular assemblies that use ATP hydrolysis to non‐covalently alter the structure of nucleosomes. Remodelers, conserved from yeast to humans, can be classified into different families based on the identity of their ATPase subunit. The diversity in their composition beyond the ATPase is reflected in the variety of outcomes of which they are capable both in vitro and in vivo : sliding of nucleosomes along DNA, ejection of histone dimers or octamers and histone dimer exchange. How do remodelers remodel chromatin? How are different products generated? Are they the result of fundamentally different mechanisms or rather of the relative fine‐tuning of a common one? We are taking a structural approach to addressing these questions, using three‐dimensional electron microscopy (3D EM), a technique well suited to the study of large, conformationally flexible complexes. Our model system is the remodeler RSC from S.cerevisiae , a ~ 1MDa 15‐subunit complex. We have obtained 3D reconstructions of RSC and have shown that it is conformationally flexible. We have proposed that a large cavity seen in the structure is the binding site for the nucleosome as it accounts for a number of biochemical observations. Our immediate goals are to map the location of RSC components as well as the actual binding site of the nucleosome in our reconstruction.