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Structural analyses of the chromatin remodelling enzymes INO80-C and SWR-C.

ABSTRACT: INO80-C and SWR-C are conserved members of a subfamily of ATP-dependent chromatin remodelling enzymes that function in transcription and genome-maintenance pathways. A crucial role for these enzymes is to control chromosomal distribution of the H2A.Z histone variant. Here we use electron microscopy (EM) and two-dimensional class averaging to demonstrate that these remodelling enzymes have similar overall architectures. Each enzyme is characterized by a dynamic 'tail' domain and a compact 'head' that contains Rvb1/Rvb2 subunits organized as hexameric rings. EM class averages and mass spectrometry support the existence of single heterohexameric rings in both SWR-C and INO80-C. EM studies define the position of the Arp8/Arp4/Act1 module within INO80-C, and we find that this module enhances nucleosome-binding affinity but is largely dispensable for remodelling activities. In contrast, the Ies6/Arp5 module is essential for INO80-C remodelling, and furthermore this module controls conformational changes that may couple nucleosome binding to remodelling.

SUBMITTER: Watanabe S

PROVIDER: S-EPMC4431590 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Structural analyses of the chromatin remodelling enzymes INO80-C and SWR-C.

Watanabe Shinya S Tan Dongyan D Lakshminarasimhan Mahadevan M Washburn Michael P MP Hong Eun-Jin Erica EJ Walz Thomas T Peterson Craig L CL

Nature communications 20150512

INO80-C and SWR-C are conserved members of a subfamily of ATP-dependent chromatin remodelling enzymes that function in transcription and genome-maintenance pathways. A crucial role for these enzymes is to control chromosomal distribution of the H2A.Z histone variant. Here we use electron microscopy (EM) and two-dimensional class averaging to demonstrate that these remodelling enzymes have similar overall architectures. Each enzyme is characterized by a dynamic 'tail' domain and a compact 'head' ...[more]

PMID: 25964121

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Project description:In the eukaryotic nucleus, DNA is packaged in the form of nucleosomes, each of which comprises about 147 base pairs of DNA wrapped around a histone protein octamer. The position and histone composition of nucleosomes is governed by ATP-dependent chromatin remodellers1-3 such as the 15-subunit INO80 complex 4 . INO80 regulates gene expression, DNA repair and replication by sliding nucleosomes, the exchange of histone H2A.Z with H2A, and the positioning of + 1 and -1 nucleosomes at promoter DNA5-8. The structures and mechanisms of these remodelling reactions are currently unknown. Here we report the cryo-electron microscopy structure of the evolutionarily conserved core of the INO80 complex from the fungus Chaetomium thermophilum bound to a nucleosome, at a global resolution of 4.3 Å and with major parts at 3.7 Å. The INO80 core cradles one entire gyre of the nucleosome through multivalent DNA and histone contacts. An Rvb1/Rvb2 AAA+ ATPase heterohexamer is an assembly scaffold for the complex and acts as a 'stator' for the motor and nucleosome-gripping subunits. The Swi2/Snf2 ATPase motor binds to nucleosomal DNA at superhelical location -6, unwraps approximately 15 base pairs, disrupts the H2A-DNA contacts and is poised to pump entry DNA into the nucleosome. Arp5 and Ies6 bind superhelical locations -2 and -3 to act as a counter grip for the motor, on the other side of the H2A-H2B dimer. The Arp5 insertion domain forms a grappler element that binds the nucleosome dyad, connects the Arp5 actin-fold and entry DNA over a distance of about 90 Å and packs against histone H2A-H2B near the 'acidic patch'. Our structure together with biochemical data 8 suggests a unified mechanism for nucleosome sliding and histone editing by INO80. The motor is part of a macromolecular ratchet, persistently pumping entry DNA across the H2A-H2B dimer against the Arp5 grip until a large nucleosome translocation step occurs. The transient exposure of H2A-H2B by motor activity as well as differential recognition of H2A.Z and H2A may regulate histone exchange.

Dataset Information

Structural analyses of the chromatin remodelling enzymes INO80-C and SWR-C.

Publications

Structural analyses of the chromatin remodelling enzymes INO80-C and SWR-C.

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