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哺乳动物 HP1 同种型在异染色质结构和组织中具有特定的作用。

Mammalian HP1 Isoforms Have Specific Roles in Heterochromatin Structure and Organization.

机构信息

Chromatin Biology Laboratory, Cancer Epigenetics and Biology Program (PEBC), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Av. Gran Via de l'Hospitalet, 199-203, 08907- L'Hospitalet de Llobregat, Barcelona, Spain; Tissue Repair and Regeneration Group, Department of Biosciences, Universitat de Vic, Universitat Central de Catalunya, Vic, Spain.

Chromatin Biology Laboratory, Cancer Epigenetics and Biology Program (PEBC), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Av. Gran Via de l'Hospitalet, 199-203, 08907- L'Hospitalet de Llobregat, Barcelona, Spain.

出版信息

Cell Rep. 2017 Nov 21;21(8):2048-2057. doi: 10.1016/j.celrep.2017.10.092.

DOI:10.1016/j.celrep.2017.10.092
PMID:29166597
Abstract

HP1 is a structural component of heterochromatin. Mammalian HP1 isoforms HP1α, HP1β, and HP1γ play different roles in genome stability, but their precise role in heterochromatin structure is unclear. Analysis of Hp1α, Hp1β, and Hp1γ MEFs show that HP1 proteins have both redundant and unique functions within pericentric heterochromatin (PCH) and also act globally throughout the genome. HP1α confines H4K20me3 and H3K27me3 to regions within PCH, while its absence results in a global hyper-compaction of chromatin associated with a specific pattern of mitotic defects. In contrast, HP1β is functionally associated with Suv4-20h2 and H4K20me3, and its loss induces global chromatin decompaction and an abnormal enrichment of CTCF in PCH and other genomic regions. Our work provides insight into the roles of HP1 proteins in heterochromatin structure and genome stability.

摘要

HP1 是异染色质的结构组成部分。哺乳动物的 HP1 同种型 HP1α、HP1β 和 HP1γ 在基因组稳定性中发挥不同的作用,但它们在异染色质结构中的精确作用尚不清楚。对 Hp1α、Hp1β 和 Hp1γ MEFs 的分析表明,HP1 蛋白在着丝粒周围异染色质 (PCH) 中具有冗余和独特的功能,并且在整个基因组中也具有全局作用。HP1α 将 H4K20me3 和 H3K27me3 局限在 PCH 内的区域,而其缺失会导致与特定有丝分裂缺陷模式相关的染色质的全局超紧缩。相比之下,HP1β 在功能上与 Suv4-20h2 和 H4K20me3 相关,其缺失会诱导全局染色质解紧缩以及 CTCF 在 PCH 和其他基因组区域的异常富集。我们的工作为 HP1 蛋白在异染色质结构和基因组稳定性中的作用提供了深入了解。

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