title: Chromatin binding and silencing: Two roles of the same protein Lem2.
abstract: Transcriptionally repressed chromatin localizes to specific areas within the eukaryotic nucleus and is often found at the nuclear periphery, which is thought to provide a specialized compartment for gene silencing. However, the molecular mechanisms that establish this spatial chromatin organization are still poorly understood. In our recent work (Barraleset al.2016), we identified the nuclear envelope protein Lem2, a homolog of metazoan lamin-associated proteins (LAPs), as a relevant factor for heterochromatin silencing and perinuclear localization in the fission yeastSchizosaccharomyces pombe. Several other LAPs have previously been reported to associate with heterochromatin, and it has been proposed that this interaction might directly contribute to gene repression, perhaps through tethering via chromatin-binding domains like the LEM domain. We demonstrated that the LEM domain of Lem2 is indeed essential for centromere binding and perinuclear tethering. However, we made the surprising finding that tethering via the LEM domain is functionally independent of Lem2's role in silencing, which instead is mediated by a different part of the protein, the MSC domain. Our study demonstrates that tethering and silencing, although mediated by the same molecule, Lem2, can be mechanistically separated. This further unveils a complex function of this protein at the interface between the nuclear periphery and silent chromatin, which might be preserved among the other members of this conserved family of LEM proteins.
authors.affiliation: Department of Physiological Chemistry, Biomedical Center, Ludwig-Maximilians-University of Munich, Grosshaderner Str. 9, 82152 Martinsried, Germany.
authors.forename: Ramón Ramos
authors.initials: RR
authors.lastname: Barrales
authors.affiliation: Department of Physiological Chemistry, Biomedical Center, Ludwig-Maximilians-University of Munich, Grosshaderner Str. 9, 82152 Martinsried, Germany.
authors.forename: Sigurd
authors.initials: S
authors.lastname: Braun
keywords: LEM; heterochromatin; lamin-associated proteins; perinuclear silencing; tethering