Scaffold attachment factor A (SAF-A) is concentrated in inactive X chromosome territories through its RGG domain
Scaffold attachment factor A (SAF-A) is concentrated in inactive X chromosome territories through its RGG domain
复制标题
DOI：
10.1007/s00412-003-0258-0
复制
发表时间：
2003-12-01
期刊：
影响因子：
1.6
通讯作者：
Fackelmayer, FO
中科院分区：
文献类型：
--
作者：
Helbig, R;Fackelmayer, FO
雌性哺乳动物细胞使其中一条X染色体的转录失活，以平衡雄性和雌性之间X连锁基因的基因表达。失活是一个多步骤的过程，涉及称为XIST的大型非编码RNA，染色质的各种表观遗传修饰以及蛋白质组成的改变，如组蛋白变体macroH2A的富集。我们在这里表明，失活的X染色体也富含核支架的一种特征明确的蛋白质成分，SAF-A。由于其对支架相关区(SAR)-DNA的高特异性，该蛋白与染色质组织有关；由于其与类固醇受体的功能相互作用，该蛋白与激素调节基因的转录调节有关；由于其与RNA和异质核核糖核蛋白（hnRNP）颗粒的相互作用，该蛋白与RNA加工有关。在几乎完全去除DNA和相关的染色质蛋白（如macroH2A）后，SAF-A仍然与“核基质”在一起，仍然突出非活性X染色体的前位置。有趣的是，在失活的X染色体上，SAF-A的富集取决于蛋白质的RNA结合域RGG盒，这提高了SAF-A与XIST RNA的相互作用可能通过核结构的局部变化导致X连锁基因沉默的可能性。
Female mammalian cells inactivate transcription from one of their X chromosomes to equalize gene expression of X-linked genes between males and females. Inactivation is a multistep process that involves a large non-coding RNA termed XIST, a variety of epigenetic modifications of chromatin, and alterations in protein composition such as enrichment of the histone variant macroH2A. We show here that inactive X chromosomes are also enriched in a well-characterized protein component of the nuclear scaffold, SAF-A. This protein has been implicated in chromatin organization, owing to its high specificity for scaffold-associated region (SAR)-DNA, in transcriptional regulation, e.g. of hormone-regulated genes, owing to its functional interaction with steroid receptors, and in RNA processing, owing to its interaction with RNA and heterogeneous nuclear ribonucleoprotein (hnRNP) particles. After near complete removal of DNA and associated chromatin proteins such as macroH2A, SAF-A remains with the "nuclear matrix", still highlighting the former position of inactive X chromosomes. Interestingly, the enrichment of SAF-A in the inactive X chromosome depends on the RNA binding domain of the protein, the RGG box, raising the possibility that interaction of SAF-A with XIST RNA may contribute to the silencing of X-linked genes by local changes in nuclear architecture.