Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Curr Opin Cell Biol. 2010 Jun;22(3):320-5. doi: 10.1016/j.ceb.2010.04.002. Epub 2010 May 3.
The nuclear lamina, a filamentous protein network that coats the inner nuclear membrane, has long been thought to interact with specific genomic loci and regulate their expression. Molecular mapping studies have now identified large genomic domains that are in contact with the lamina. Genes in these domains are typically repressed, and artificial tethering experiments indicate that the lamina can actively contribute to this repression. Furthermore, the lamina indirectly controls gene expression in the nuclear interior by sequestration of certain transcription factors. A variety of DNA-binding and chromatin proteins may anchor specific loci to the lamina, while histone-modifying enzymes partly mediate the local repressive effect of the lamina. Experimental tools are now available to begin to unravel the underlying molecular mechanisms.
核纤层是一种丝状的蛋白网络,覆盖在内核膜的内表面,长期以来一直被认为与特定的基因组位置相互作用并调节它们的表达。分子作图研究现在已经鉴定出与核纤层接触的大的基因组区域。这些区域中的基因通常被抑制,人工系缚实验表明核纤层可以主动促成这种抑制。此外,核纤层通过隔离某些转录因子间接控制核内的基因表达。各种 DNA 结合蛋白和染色质蛋白可能将特定的位置锚定在核纤层上,而组蛋白修饰酶部分介导核纤层的局部抑制作用。现在已经有实验工具来开始揭示潜在的分子机制。