Coordinated methyl and RNA binding is required for heterochromatin localization of mammalian HP1α

Coordinated methyl and RNA binding is required for heterochromatin localization of mammalian HP1α
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DOI:
10.1093/embo-reports/kvf194
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发表时间:
2002-10-01
期刊:
影响因子:
7.7
通讯作者:
Yaniv, M
Yaniv, M
中科院分区:
生物学2区
文献类型:
--
作者:
Muchardt, C;Guillemé, M;Yaniv, M

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在哺乳动物细胞中,如裂糖菌和果蝇,HP1蛋白结合在赖氨酸9 (K9)甲基化的组蛋白H3尾部。然而,k9甲基化的H3组蛋白分布在整个细胞核中,而HP1蛋白则富集在中心周围异染色质中。这一观察结果表明,HP1的甲基结合特性可能不足以实现其异染色质靶向。我们发现,HP1与周围中心异染色质的关联不仅取决于其甲基结合的染色质结构域,还取决于连接保守的染色质和色影结构域的蛋白质铰链区域中存在的rna结合活性。我们的数据表明存在由甲基化组蛋白H3尾部和RNA组成的复杂异染色质结合位点,每个位点都被hp1α的单独结构域识别。
In mammalian cells, as in Schizosaccharomyces pombe and Drosophila, HP1 proteins bind histone H3 tails methylated on lysine 9 (K9). However, whereas K9-methylated H3 histones are distributed throughout the nucleus, HP1 proteins are enriched in pericentromeric heterochromatin. This observation suggests that the methyl-binding property of HP1 may not be sufficient for its heterochromatin targeting. We show that the association of HP1 with pericentromeric heterochromatin depends not only on its methyl-binding chromo domain but also on an RNA-binding activity present in the hinge region of the protein that connects the conserved chromo and chromoshadow domains. Our data suggest the existence of complex heterochromatin binding sites composed of methylated histone H3 tails and RNA, with each being recognized by a separate domain of HP1alpha.