Linker Histone H1.2 Directs Genome-wide Chromatin Association of the Retinoblastoma Tumor Suppressor Protein and Facilitates Its Function.
Linker Histone H1.2 Directs Genome-wide Chromatin Association of the Retinoblastoma Tumor Suppressor Protein and Facilitates Its Function.
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DOI：
10.1016/j.celrep.2017.05.053
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发表时间：
2017-06-13
期刊：
影响因子：
8.8
通讯作者：
La Thangue NB
中科院分区：
文献类型：
--
作者：
Munro S;Hookway ES;Floderer M;Carr SM;Konietzny R;Kessler BM;Oppermann U;La Thangue NB
视网膜母细胞瘤肿瘤抑制蛋白pRb是细胞增殖的主要调节因子，主要通过与E2 F相互作用和调节E2 F靶基因。在这里，我们描述的H1.2连接组蛋白作为一个主要的pRb相互作用的合作伙伴。我们确定H1.2和pRb在不同E2 F靶基因上的染色质结合复合物中被发现。询问H1.2对pRb全基因组分布的全球影响表明，受H1.2影响的E2 F靶基因在功能上与细胞周期控制相关，这与H1.2阻碍细胞增殖的能力和生长停滞细胞中发生的染色质结合H1-pRb复合物水平升高一致。我们的研究结果定义了一个网络的E2 F靶基因作为易受H1.2的调控影响，其中H1.2增强全球协会的pRb与染色质，增强转录抑制pRb，并促进pRb依赖的细胞周期阻滞。H1.2接头组蛋白是pRb相互作用的主要和重要的伴侣H1.2，pRb位于不同E2 F靶基因上的染色质结合复合物中，H1.2影响pRb的整体染色质缔合和全基因组分布，H1.2增强pRb的转录抑制，并促进细胞周期停滞Munro et al.证明pRb与连接体组蛋白H1.2相互作用。pRb-H1.2复合物富集在与细胞周期控制相关的E2 F靶基因子集的染色质上。此外，H1.2影响pRb的全基因组染色质结合特性，并影响转录抑制和细胞周期控制。
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. The H1.2 linker histone is a major and significant pRb interaction partner H1.2 and pRb reside in a chromatin-bound complex on diverse E2F target genes H1.2 influences global chromatin association and genome-wide distribution of pRb H1.2 enhances transcriptional repression by pRb and facilitates cell-cycle arrest 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.