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

Publication date: 13 June 2017
Source:Cell Reports, Volume 19, Issue 11
Author(s): Shonagh Munro, Edward S. Hookway, Melanie Floderer, Simon M. Carr, Rebecca Konietzny, Benedikt M. Kessler, Udo Oppermann, Nicholas B. La Thangue
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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Teaser

Munro et al. demonstrate that pRb interacts with linker histone H1.2. The pRb-H1.2 complex is enriched on the chromatin of a subset of E2F target genes associated with cell-cycle control. Moreover, H1.2 influences the genome-wide chromatin-binding properties of pRb and impacts transcriptional repression and cell-cycle control.


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