State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
J Cell Sci. 2010 Aug 15;123(Pt 16):2853-61. doi: 10.1242/jcs.063610. Epub 2010 Jul 27.
Chromatin assembly factor 1 (CAF-1) was initially characterized as a histone deliver in the process of DNA-replication-coupled chromatin assembly in eukaryotic cells. Here, we report that CAF-1 p180, the largest subunit of Drosophila CAF-1, participates in the process of heterochromatin formation and functions to maintain pericentric heterochromatin stability. We provide evidence that Drosophila CAF-1 p180 plays a role in both classes of position effect variegation (PEV) and in the expression of heterochromatic genes. A decrease in the expression of Drosophila CAF-1 p180 leads to a decrease in both H3K9 methylation at pericentric heterochromatin regions and the recruitment of heterochromatin protein 1 (HP1) to the chromocenter of the polytene chromosomes. The artificial targeting of HP1 to a euchromatin location leads to the enrichment of Drosophila CAF-1 p180 at this ectopic heterochromatin, suggesting the mutual recruitment of HP1 and CAF-1 p180. We also show that the spreading of heterochromatin is compromised in flies that have reduced CAF-1 p180. Furthermore, reduced CAF-1 p180 causes a defect in the dynamics of heterochromatic markers in early Drosophila embryos. Together, these findings suggest that Drosophila CAF-1 p180 is an essential factor in the epigenetic control of heterochromatin formation and/or maintenance.
染色质组装因子 1(CAF-1)最初被描述为在真核细胞 DNA 复制偶联的染色质组装过程中输送组蛋白的因子。在这里,我们报告说果蝇 CAF-1 的最大亚基 CAF-1 p180 参与异染色质形成过程,并维持着着丝粒异染色质的稳定性。我们提供的证据表明,果蝇 CAF-1 p180 参与了两类位置效应(PEV)的发生和异染色质基因的表达。果蝇 CAF-1 p180 的表达减少会导致着丝粒异染色质区域的 H3K9 甲基化减少和异染色质蛋白 1(HP1)向多线染色体着丝粒中心的募集减少。将 HP1 人为靶向到常染色质位置会导致果蝇 CAF-1 p180 在此异位异染色质处的富集,表明 HP1 和 CAF-1 p180 之间的相互募集。我们还表明,在 CAF-1 p180 减少的果蝇中,异染色质的扩散受到了损害。此外,CAF-1 p180 的减少会导致早期果蝇胚胎中异染色质标记的动态变化出现缺陷。综上所述,这些发现表明果蝇 CAF-1 p180 是异染色质形成和/或维持的表观遗传控制的一个重要因素。