Lamin B Receptor Recognizes Specific Modifications of Histone H4 in Heterochromatin Formation
Lamin B Receptor Recognizes Specific Modifications of Histone H4 in Heterochromatin Formation
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DOI：
10.1074/jbc.m112.397950
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发表时间：
2012-12-14
影响因子：
4.8
通讯作者：
Hiraoka, Yasushi
中科院分区：
文献类型：
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作者：
Hirano, Yasuhiro;Hizume, Kohji;Hiraoka, Yasushi
内核膜蛋白为染色质提供结构框架，调节核膜下的转录。核纤层蛋白B受体（Lamin B receptor，LBR）是一种典型的与异染色质结合的核内膜蛋白，其突变可导致人类Pelger-Huet异常。然而，LBR组织异染色质的机制仍有待阐明。在这里，我们表明，LBR抑制转录结合染色质区域，标记的特定组蛋白修饰。LBR的tudor结构域（残基1-62）主要识别组蛋白H4赖氨酸20二甲基化，并且对于染色质致密化至关重要，而整个核质区域（残基1-211）是转录抑制所需的。我们提出了一个模型，在该模型中，LBR的核质结构域系留表观遗传标记的染色质的核膜和转录抑制因子加载到染色质上，通过它们与LBR的相互作用。
Inner nuclear membrane proteins provide a structural framework for chromatin, modulating transcription beneath the nuclear envelope. Lamin B receptor (LBR) is a classical inner nuclear membrane protein that associates with heterochromatin, and its mutations are known to cause Pelger-Huet anomaly in humans. However, the mechanisms by which LBR organizes heterochromatin remain to be elucidated. Here, we show that LBR represses transcription by binding to chromatin regions that are marked by specific histone modifications. The tudor domain (residues 1-62) of LBR primarily recognizes histone H4 lysine 20 dimethylation and is essential for chromatin compaction, whereas the whole nucleoplasmic region (residues 1-211) is required for transcriptional repression. We propose a model in which the nucleoplasmic domain of LBR tethers epigenetically marked chromatin to the nuclear envelope and transcriptional repressors are loaded onto the chromatin through their interaction with LBR.