title: Lamin B receptor recognizes specific modifications of histone H4 in heterochromatin formation.
abstract: 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.
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Yamadaoka 1-3, Suita, Osaka 565-0871, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hirano
authors.forename: Kohji
authors.initials: K
authors.lastname: Hizume
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Kunio
authors.initials: K
authors.lastname: Takeyasu
authors.forename: Tokuko
authors.initials: T
authors.lastname: Haraguchi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hiraoka
mesh_terms: D000595:Amino Acid Sequence; D057809:HEK293 Cells; D006367:HeLa Cells; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D034921:Lamin Type B / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008954:Models, Biological; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D000097682:Lamin B Receptor
chemical_list: D006570:Heterochromatin; D006657:Histones; D034921:Lamin Type B; D008239:Lysine; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D000097682:Lamin B Receptor