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首页> 外文期刊>Nucleus >Association of ORCA/LRWD1 with repressive histone methyl transferases mediates heterochromatin organization
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Association of ORCA/LRWD1 with repressive histone methyl transferases mediates heterochromatin organization

机译：ORCA / LRWD1与抑制性组蛋白甲基转移酶的介导异染色质组织。

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摘要

Heterochromatin mostly constitutes tightly packaged DNA, decorated with repressive histone marks, including histone H3 methylated at lysine 9, histone H4 methylated at lysine 20 and histone H3 methylated at lysine 27. Each of these marks is incorporated by specific histone lysine methyl transferases. While constitutive heterochromatin enriched with H3K9me3 and H4K20me3 occur within repetitive elements, including centromeres and telomeres, the facultative heterochromatin resides on the inactive X-chromosome and contains H3K27me3 mark. Origin recognition complex-associated (ORCA/LRWD1) protein is required for the initiation of DNA replication and also plays crucial roles in heterochromatin organization. ORCA associates with constitutive and facultative heterochromatin in human cells and binds to repressive histone marks. We demonstrate that ORCA binds to multiple repressive histone methyl transferases including G9a, GLP, Suv39h1 (H3K9me2/3), Suv420h1/h2 (H4K20me2/3) and EZH2 (H3K27me3). Removal of ORCA from human cells causes aberrations in the chromatin architecture. We propose that ORCA acts as a scaffold protein that enables the formation of multiple histone lysine methyltransferase complexes at heterochromatic sites thereby facilitating chromatin organization.
机译：异染色质主要构成紧密包装的DNA，并带有抑制性的组蛋白标记，包括在赖氨酸9处甲基化的组蛋白H3在赖氨酸20处甲基化的组蛋白H4和在赖氨酸27处甲基化的组蛋白H3。这些标记中的每一个都通过特定的组蛋白赖氨酸甲基转移酶掺入。虽然富含H3K9me3和H4K20me3的组成型异染色质出现在包括着丝粒和端粒的重复元素内，但兼性异染色质驻留在非活性X染色体上，并含有H3K27me3标记。起始识别复合物相关（ORCA / LRWD1）蛋白是DNA复制启动所必需的，并且在异染色质组织中也起着至关重要的作用。 ORCA与人类细胞中的组成型和兼性异染色质结合，并与阻抑组蛋白标记结合。我们证明ORCA绑定到多个阻遏组蛋白甲基转移酶，包括G9a，GLP，Suv39h1（H3K9me2 / 3），Suv420h1 / h2（H4K20me2 / 3）和EZH2（H3K27me3）。从人细胞中去除ORCA会导致染色质结构异常。我们提出，ORCA作为一种支架蛋白，能够在异色位点形成多个组蛋白赖氨酸甲基转移酶复合物，从而促进染色质的组织。

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