Lamin B Receptor Recognizes Specific Modifications of Histone H4 in Heterochromatin Formation

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.