Linker Histone H1.2 Directs Genome-wide Chromatin Association of the Retinoblastoma Tumor Suppressor Protein and Facilitates Its Function.

Autor:	Munro S; Laboratory of Cancer Biology, Medical Sciences Division, Department of Oncology, University of Oxford, Old Road Campus Research Building, Old Road Campus, Oxford OX3 7DQ, UK., Hookway ES; Nuffield Orthopaedic Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Oxford OX3 7HE, UK., Floderer M; Laboratory of Cancer Biology, Medical Sciences Division, Department of Oncology, University of Oxford, Old Road Campus Research Building, Old Road Campus, Oxford OX3 7DQ, UK., Carr SM; Laboratory of Cancer Biology, Medical Sciences Division, Department of Oncology, University of Oxford, Old Road Campus Research Building, Old Road Campus, Oxford OX3 7DQ, UK., Konietzny R; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, UK., Kessler BM; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, UK., Oppermann U; Nuffield Orthopaedic Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Oxford OX3 7HE, UK., La Thangue NB; Laboratory of Cancer Biology, Medical Sciences Division, Department of Oncology, University of Oxford, Old Road Campus Research Building, Old Road Campus, Oxford OX3 7DQ, UK. Electronic address: nick.lathangue@oncology.ox.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2017 Jun 13; Vol. 19 (11), pp. 2193-2201.
DOI:	10.1016/j.celrep.2017.05.053
Abstrakt:	The retinoblastoma tumor suppressor protein pRb is a master regulator of cellular proliferation, principally through interaction with E2F and regulation of E2F target genes. Here, we describe the H1.2 linker histone as a major pRb interaction partner. We establish that H1.2 and pRb are found in a chromatin-bound complex on diverse E2F target genes. Interrogating the global influence of H1.2 on the genome-wide distribution of pRb indicated that the E2F target genes affected by H1.2 are functionally linked to cell-cycle control, consistent with the ability of H1.2 to hinder cell proliferation and the elevated levels of chromatin-bound H1-pRb complex, which occur in growth-arrested cells. Our results define a network of E2F target genes as susceptible to the regulatory influence of H1.2, where H1.2 augments global association of pRb with chromatin, enhances transcriptional repression by pRb, and facilitates pRb-dependent cell-cycle arrest. (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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