Huang Shengbing, Zhou Hui, Tarara Jim, Zhang Zhiguo
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
EMBO J. 2007 May 2;26(9):2274-83. doi: 10.1038/sj.emboj.7601670. Epub 2007 Apr 5.
The histone chaperones CAF-1 and Rtt106p are required for heterochromatin silencing in the yeast Saccharomyces cerevisiae. Although it has been suggested that CAF-1 is involved in the maintenance of heterochromatin silencing, their exact functions during this process are not well understood. Here, we show that CAF-1 and Rtt106p are involved in the early stages of heterochromatin formation. The binding of Sir proteins to telomeric heterochromatin is significantly reduced and, additionally, Sir proteins are mislocalized in cells lacking CAF-1 and Rtt106p. At the HMR locus, CAF-1 and Rtt106p are required for the initial recruitment of Sir2p and Sir3p, but not Sir4p, to the HMR-E silencer, where silencing initiates, as well as the efficient spreading of all of these Sir proteins to the distal a1 gene. Moreover, silencing at the HMR locus is dramatically reduced in cells lacking CAF-1, Rtt106p, and Sir1p. Thus, these studies reveal a novel role for CAF-1 and Rtt106p in epigenetic silencing and indicate that the spreading of heterochromatin, a poorly understood process, requires histone chaperones.
组蛋白伴侣CAF-1和Rtt106p是酿酒酵母中异染色质沉默所必需的。尽管有人提出CAF-1参与异染色质沉默的维持，但在此过程中它们的确切功能尚不清楚。在这里，我们表明CAF-1和Rtt106p参与异染色质形成的早期阶段。Sir蛋白与端粒异染色质的结合显著减少，此外，Sir蛋白在缺乏CAF-1和Rtt106p的细胞中定位错误。在HMR位点，CAF-1和Rtt106p是Sir2p和Sir3p（而非Sir4p）最初募集到沉默起始的HMR-E沉默子以及所有这些Sir蛋白有效扩散到远端a1基因所必需的。此外，在缺乏CAF-1、Rtt106p和Sir1p的细胞中，HMR位点的沉默显著降低。因此，这些研究揭示了CAF-1和Rtt106p在表观遗传沉默中的新作用，并表明异染色质扩散这一理解不足的过程需要组蛋白伴侣。
