Barrales Ramón Ramos, Braun Sigurd
Department of Physiological Chemistry, Biomedical Center, Ludwig-Maximilians-University of Munich, Grosshaderner Str. 9, 82152 Martinsried, Germany.
Microb Cell. 2016 Apr 4;3(4):185-188. doi: 10.15698/mic2016.04.495.
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 (Barrales 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 yeast . 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.
转录抑制的染色质定位于真核细胞核内的特定区域，且常位于核周，人们认为这为基因沉默提供了一个特殊的区域。然而，建立这种空间染色质组织的分子机制仍知之甚少。在我们最近的工作（Barrales 2016）中，我们鉴定出核膜蛋白Lem2，它是后生动物核纤层相关蛋白（LAPs）的同源物，是裂殖酵母中异染色质沉默和核周定位的一个相关因子。此前已有报道称，其他几种LAPs与异染色质相关，并且有人提出这种相互作用可能直接导致基因抑制，也许是通过像LEM结构域这样的染色质结合结构域进行 tethering（此处tethering 暂未找到合适中文释义，保留英文）。我们证明Lem2的LEM结构域确实对于着丝粒结合和核周 tethering 至关重要。然而，我们有一个惊人的发现，即通过LEM结构域的tethering在功能上独立于Lem2在沉默中的作用，后者反而由该蛋白的不同部分即MSC结构域介导。我们的研究表明，尽管tethering和沉默由同一分子Lem2介导，但在机制上可以分开。这进一步揭示了该蛋白在核周和沉默染色质之间界面处的复杂功能，这可能在这个保守的LEM蛋白家族的其他成员中也得以保留。
