Braun Sigurd, Barrales Ramón Ramos
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.
Nucleus. 2016 Nov;7(6):523-531. doi: 10.1080/19491034.2016.1252892. Epub 2016 Oct 31.
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. We 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.
核膜在染色质的功能组织中起着关键作用。各种内核膜（INM）蛋白与转录抑制的染色质相关联，这种染色质常位于核周。一个突出的例子是LEM（LAP2 - Emerin - MAN1）结构域蛋白的保守家族，它们与DNA结合蛋白相互作用，并被认为介导染色质与核膜的连接。我们最近报道，裂殖酵母蛋白Lem2是后生动物LEM蛋白的同源物，它有助于异染色质的核周定位和沉默。我们证明着丝粒染色质的结合和连接取决于Lem2的LEM结构域。出乎意料的是，该结构域对于异染色质沉默是可有可无的，而异染色质沉默是由Lem2的另一个结构域，即MSC（MAN1 - Src1 C末端）结构域介导的。因此，Lem2的沉默和连接在机制上可以分开。值得注意的是，MSC结构域除了异染色质沉默外还有多种功能。在这里，我们讨论这些新发现对理解这种保守的INM蛋白的意义。
