Graduate School of Frontier Biosciences, Osaka University, Yamadaoka 1-3, Suita, Osaka 565-0871, Japan.
J Biol Chem. 2012 Dec 14;287(51):42654-63. doi: 10.1074/jbc.M112.397950. Epub 2012 Oct 25.
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-Huët 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.
核内层膜蛋白为染色质提供了一个结构框架，调节核膜下的转录。核膜层蛋白 B 受体（LBR）是一种经典的核内层膜蛋白，与异染色质相关联，其突变已知会导致人类佩尔格-胡特异常。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 通过与特定组蛋白修饰标记的染色质区域结合来抑制转录。LBR 的结构域（残基 1-62）主要识别组蛋白 H4 赖氨酸 20 二甲基化，对于染色质的紧缩是必需的，而整个核质区域（残基 1-211）对于转录抑制是必需的。我们提出了一个模型，即 LBR 的核质域将表观遗传标记的染色质束缚在核膜上，转录抑制剂通过与 LBR 的相互作用被加载到染色质上。
