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Dinucleosome specificity and allosteric switch of the ISW1a ATP-dependent chromatin remodeler in transcription regulation

Saurabh K. Bhardwaj, Solomon G. Hailu, Lola Olufemi, Sandipan Brahma, Soumyadipta Kundu, Swetansu K. Hota, Jim Persinger and Blaine Bartholomew ()
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Saurabh K. Bhardwaj: Department of Epigenetics & Molecular Carcinogenesis, Science Park
Solomon G. Hailu: Department of Epigenetics & Molecular Carcinogenesis, Science Park
Lola Olufemi: National Institute of Neurological Disorders and Stroke
Sandipan Brahma: Department of Epigenetics & Molecular Carcinogenesis, Science Park
Soumyadipta Kundu: Department of Epigenetics & Molecular Carcinogenesis, Science Park
Swetansu K. Hota: Gladstone Institutes
Jim Persinger: Department of Epigenetics & Molecular Carcinogenesis, Science Park
Blaine Bartholomew: Department of Epigenetics & Molecular Carcinogenesis, Science Park

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Over the last 3 decades ATP-dependent chromatin remodelers have been thought to recognize chromatin at the level of single nucleosomes rather than higher-order organization of more than one nucleosome. We show the yeast ISW1a remodeler has such higher-order structural specificity, as manifested by large allosteric changes that activate the nucleosome remodeling and spacing activities of ISW1a when bound to dinucleosomes. Although the ATPase domain of Isw1 docks at the SHL2 position when ISW1a is bound to either mono- or di-nucleosomes, there are major differences in the interactions of the catalytic subunit Isw1 with the acidic pocket of nucleosomes and the accessory subunit Ioc3 with nucleosomal DNA. By mutational analysis and uncoupling of ISW1a’s dinucleosome specificity, we find that dinucleosome recognition is required by ISW1a for proper chromatin organization at promoters; as well as transcription regulation in combination with the histone acetyltransferase NuA4 and histone H2A.Z exchanger SWR1.

Date: 2020
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DOI: 10.1038/s41467-020-19700-1

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