Munro, S; Hookway, ES; Floderer, M; Carr, SM; Konietzny, R; Kessler, BM; Oppermann, U; Munro, S; Hookway, ES; Floderer, M; Carr, SM; Konietzny, R; Kessler, BM; Oppermann, U; La Thangue, NB; - view fewer (2017) Linker Histone H1.2 Directs Genome-wide Chromatin Association of the Retinoblastoma Tumor Suppressor Protein and Facilitates Its Function. Cell Reports , 19 (11) pp. 2193-2201. 10.1016/j.celrep.2017.05.053.

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Abstract

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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