Grund Stefanie E, Fischer Tamás, Cabal Ghislain G, Antúnez Oreto, Pérez-Ortín José E, Hurt Ed
Biochemie-Zentrum der Universität Heidelberg, D-69120 Heidelberg, Germany.
J Cell Biol. 2008 Sep 8;182(5):897-910. doi: 10.1083/jcb.200803098. Epub 2008 Sep 1.
Inner nuclear membrane proteins containing a LEM (LAP2, emerin, and MAN1) domain participate in different processes, including chromatin organization, gene expression, and nuclear envelope biogenesis. In this study, we identify a robust genetic interaction between transcription export (TREX) factors and yeast Src1, an integral inner nuclear membrane protein that is homologous to vertebrate LEM2. DNA macroarray analysis revealed that the expression of the phosphate-regulated genes PHO11, PHO12, and PHO84 is up-regulated in src1Delta cells. Notably, these PHO genes are located in subtelomeric regions of chromatin and exhibit a perinuclear location in vivo. Src1 spans the nuclear membrane twice and exposes its N and C domains with putative DNA-binding motifs to the nucleoplasm. Genome-wide chromatin immunoprecipitation-on-chip analyses indicated that Src1 is highly enriched at telomeres and subtelomeric regions of the yeast chromosomes. Our data show that the inner nuclear membrane protein Src1 functions at the interface between subtelomeric gene expression and TREX-dependent messenger RNA export through the nuclear pore complexes.
含有LEM（LAP2、emerin和MAN1）结构域的内核膜蛋白参与不同的过程，包括染色质组织、基因表达和核膜生物发生。在本研究中，我们确定了转录输出（TREX）因子与酵母Src1之间存在强大的遗传相互作用，Src1是一种内核膜整合蛋白，与脊椎动物LEM2同源。DNA微阵列分析显示，磷酸盐调节基因PHO11、PHO12和PHO84在src1Delta细胞中的表达上调。值得注意的是，这些PHO基因位于染色质的亚端粒区域，并且在体内呈现核周定位。Src1跨核膜两次，将其带有假定DNA结合基序的N和C结构域暴露于核质中。全基因组芯片染色质免疫沉淀分析表明，Src1在酵母染色体的端粒和亚端粒区域高度富集。我们的数据表明，内核膜蛋白Src1在亚端粒基因表达与通过核孔复合体的TREX依赖性信使RNA输出之间的界面发挥作用。
