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

• Published in: The Journal of biological chemistry Vol. 287; no. 51; pp. 42654 - 42663
• Main Authors: Hirano, Yasuhiro, Hizume, Kohji, Kimura, Hiroshi, Takeyasu, Kunio, Haraguchi, Tokuko, Hiraoka, Yasushi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14-12-2012; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Chromatin; Chromatin Histone Modification; Chromatin Organization; DNA and Chromosomes; HEK293 Cells; HeLa Cells; Heterochromatin; Heterochromatin - metabolism; Histone Code; Histones - metabolism; Humans; Lamin B Receptor; Lamin Type B - metabolism; Lysine - metabolism; Methylation; Models, Biological; Molecular Sequence Data; Nuclear Envelope; Nuclear Envelope - metabolism; Nuclear Membrane; Nuclear Organization; Protein Binding; Protein Multimerization; Protein Processing, Post-Translational; Protein Structure, Tertiary; Receptors, Cytoplasmic and Nuclear - chemistry; Receptors, Cytoplasmic and Nuclear - metabolism; Repressor Proteins - metabolism; Transcription, Genetic; Tudor Domain; Chromatin Histone Modification; Chromatin; Heterochromatin; Nuclear Membrane; Lamin B Receptor; Chromatin Organization; Histone Code; Nuclear Organization; Nuclear Envelope; Tudor Domain
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M112.397950

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.
Background: LBR is an inner nuclear membrane protein that participates in heterochromatin organization.
Results: LBR recognizes specific histone modifications and induces chromatin compaction and transcriptional repression.
Conclusion: LBR tethers epigenetically marked chromatin to the NE to repress transcription.
Significance: This finding provides an implication of how transcriptional activities are repressed beneath the NE.