title: Beyond Tethering and the LEM domain: MSCellaneous functions of the inner nuclear membrane Lem2.
abstract: The nuclear envelope plays a pivotal role in the functional organization of chromatin. Various inner nuclear membrane (INM) proteins associate with transcriptionally repressed chromatin, which is often found at the nuclear periphery. A prominent example is the conserved family of LEM (LAP2-Emerin-MAN1) domain proteins that interact with DNA-binding proteins and have been proposed to mediate tethering of chromatin to the nuclear membrane. We recently reported that the fission yeast protein Lem2, a homolog of metazoan LEM proteins, contributes to perinuclear localization and silencing of heterochromatin.1We demonstrate that binding and tethering of centromeric chromatin depends on the LEM domain of Lem2. Unexpectedly, this domain is dispensable for heterochromatin silencing, which is instead mediated by a different structural domain of Lem2, the MSC (MAN1-Src1 C-terminal) domain. Hence, silencing and tethering by Lem2 can be mechanistically separated. Notably, the MSC domain has multiple functions beyond heterochromatic silencing. Here we discuss the implications of these novel findings for the understanding of this conserved INM protein.
authors: a Department of Physiological Chemistry , Biomedical Center (BMC), Ludwig-Maximilians-University of Munich , Martinsried , Germany.
authors: Sigurd
authors: S
authors: Braun
authors: a Department of Physiological Chemistry , Biomedical Center (BMC), Ludwig-Maximilians-University of Munich , Martinsried , Germany.|b Present address: Centro Andaluz de Biología del Desarrollo. Universidad Pablo de Olavide, Sevilla-CSIC-Junta de Andalucía , Sevilla , Spain.
authors: Ramón Ramos
authors: RR
authors: Barrales
mesh_terms: D000818:Animals; D020868:Gene Silencing; D006801:Humans; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D000072417:Protein Domains; D021381:Protein Transport
chemical_list: D009687:Nuclear Proteins
keywords: LEM domain; MSC domain; chromatin tethering; heterochromatin; perinuclear silencing