Histone Octamer Structure Is Altered Early in ISW2 ATP-Dependent Nucleosome Remodeling
Arjan Hada,
Swetansu K. Hota,
Jie Luo,
Yuan-chi Lin,
Seyit Kale,
Alexey K. Shaytan,
Saurabh K. Bhardwaj,
Jim Persinger,
Jeff Ranish,
Anna R. Panchenko,
Blaine Bartholomew
Affiliations
Arjan Hada
Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center – Science Park, Smithville, TX 78957, USA; Catalent Pharma Solutions, 726 Heartland Trail, Madison, WI 53717, USA
Swetansu K. Hota
Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center – Science Park, Smithville, TX 78957, USA
Jie Luo
Institute for Systems Biology, Seattle, WA 98109, USA
Yuan-chi Lin
Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center – Science Park, Smithville, TX 78957, USA
Seyit Kale
Computational Biology Branch, National Center for Biotechnology Information National Library of Medicine, NIH, Bethesda, MD 20894, USA
Alexey K. Shaytan
Computational Biology Branch, National Center for Biotechnology Information National Library of Medicine, NIH, Bethesda, MD 20894, USA; Department of Biology, Lomonosov Moscow State University, Moscow 119991, Russia
Saurabh K. Bhardwaj
Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center – Science Park, Smithville, TX 78957, USA; BioTherapeutics Pharmaceutical Sciences, Bioprocess Research & Development, Pfizer, 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA
Jim Persinger
Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center – Science Park, Smithville, TX 78957, USA
Jeff Ranish
Institute for Systems Biology, Seattle, WA 98109, USA
Anna R. Panchenko
Computational Biology Branch, National Center for Biotechnology Information National Library of Medicine, NIH, Bethesda, MD 20894, USA
Blaine Bartholomew
Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center – Science Park, Smithville, TX 78957, USA; Corresponding author
Summary: Nucleosomes are the fundamental building blocks of chromatin that regulate DNA access and are composed of histone octamers. ATP-dependent chromatin remodelers like ISW2 regulate chromatin access by translationally moving nucleosomes to different DNA regions. We find that histone octamers are more pliable than previously assumed and distorted by ISW2 early in remodeling before DNA enters nucleosomes and the ATPase motor moves processively on nucleosomal DNA. Uncoupling the ATPase activity of ISW2 from nucleosome movement with deletion of the SANT domain from the C terminus of the Isw2 catalytic subunit traps remodeling intermediates in which the histone octamer structure is changed. We find restricting histone movement by chemical crosslinking also traps remodeling intermediates resembling those seen early in ISW2 remodeling with loss of the SANT domain. Other evidence shows histone octamers are intrinsically prone to changing their conformation and can be distorted merely by H3-H4 tetramer disulfide crosslinking. : Hada et al. show that ISW2 catalyzes DNA movement through nucleosomes with a short stretch of DNA persistently exiting the nucleosome before DNA enters nucleosomes. A consequence of asynchronous DNA movement is distortion of the histone octamer structure in which the rotational phasing of DNA is maintained on the octamer surface. Keywords: ISWI, nucleosome dynamics, nucleosome structure, SANT domain, chromatin remodeling, nucleosome movement, histones, gene regulation, transcription
