Mammalian HP1 Isoforms Have Specific Roles in Heterochromatin Structure and Organization
Mammalian HP1 Isoforms Have Specific Roles in Heterochromatin Structure and Organization
复制标题
哺乳动物 HP1 同工酶在异染色质结构和组织中发挥特殊作用
DOI：
10.1016/j.celrep.2017.10.092
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发表时间：
2017-11-21
期刊：
影响因子：
8.8
通讯作者：
Vaquero, Alejandro
中科院分区：
文献类型：
--
作者：
Bosch-Presegue, Laia;Raurell-Vila, Helena;Vaquero, Alejandro
HP 1是异染色质的结构组分。哺乳动物HP 1亚型HP 1 α、HP 1 β和HP 1 γ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确切作用尚不清楚。对Hp 1 alpha（-/-）、Hp 1 beta（-/-）和Hp 1 gamma（-/-）MEF的分析表明，HP 1蛋白在臂间异染色质（PCH）内具有冗余和独特的功能，并且在整个基因组中全局起作用。HP 1a将H4 K20 me 3和H3 K27 me 3限制在PCH内的区域，而其缺失导致与特定模式的有丝分裂缺陷相关的染色质的整体超致密化。相比之下，HP 1b在功能上与Suv 4 - 20 h2和H4 K20 me 3相关，并且其丢失诱导全局染色质解压缩以及PCH和其他基因组区域中CTCF的异常富集。我们的工作提供了深入了解HP 1蛋白在异染色质结构和基因组稳定性中的作用。
HP1 is a structural component of heterochromatin. Mammalian HP1 isoforms HP1 alpha, HP1 beta, and HP1 gamma play different roles in genome stability, but their precise role in heterochromatin structure is unclear. Analysis of Hp1 alpha(-/-), Hp1 beta(-/-), and Hp1 gamma(-/-) MEFs show that HP1 proteins have both redundant and unique functions within pericentric heterochromatin (PCH) and also act globally throughout the genome. HP1a 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, HP1b 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.