Linker histone H1.2 directs genome-wide chromatin association of the retinoblastoma tumor suppressor protein and facilitates its function

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 ch...

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Главные авторы: Munro, S, Hookway, E, Floderer, M, Carr, S, Konietzny, R, Kessler, B, Oppermann, U, La Thangue, N
Формат: Journal article
Язык:English
Опубликовано: Elsevier 2017
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author Munro, S
Hookway, E
Floderer, M
Carr, S
Konietzny, R
Kessler, B
Oppermann, U
La Thangue, N
author_facet Munro, S
Hookway, E
Floderer, M
Carr, S
Konietzny, R
Kessler, B
Oppermann, U
La Thangue, N
author_sort Munro, S
collection OXFORD
description 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.
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spelling oxford-uuid:bccc314f-b1e3-47be-ab6a-a6b7cfbeeb792022-03-27T05:27:07ZLinker histone H1.2 directs genome-wide chromatin association of the retinoblastoma tumor suppressor protein and facilitates its functionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bccc314f-b1e3-47be-ab6a-a6b7cfbeeb79EnglishSymplectic Elements at OxfordElsevier2017Munro, SHookway, EFloderer, MCarr, SKonietzny, RKessler, BOppermann, ULa Thangue, NThe 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.
spellingShingle Munro, S
Hookway, E
Floderer, M
Carr, S
Konietzny, R
Kessler, B
Oppermann, U
La Thangue, N
Linker histone H1.2 directs genome-wide chromatin association of the retinoblastoma tumor suppressor protein and facilitates its function
title Linker histone H1.2 directs genome-wide chromatin association of the retinoblastoma tumor suppressor protein and facilitates its function
title_full Linker histone H1.2 directs genome-wide chromatin association of the retinoblastoma tumor suppressor protein and facilitates its function
title_fullStr Linker histone H1.2 directs genome-wide chromatin association of the retinoblastoma tumor suppressor protein and facilitates its function
title_full_unstemmed Linker histone H1.2 directs genome-wide chromatin association of the retinoblastoma tumor suppressor protein and facilitates its function
title_short Linker histone H1.2 directs genome-wide chromatin association of the retinoblastoma tumor suppressor protein and facilitates its function
title_sort linker histone h1 2 directs genome wide chromatin association of the retinoblastoma tumor suppressor protein and facilitates its function
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