Walfridsson Julian, Bjerling Pernilla, Thalen Maria, Yoo Eung-Jae, Park Sang Dai, Ekwall Karl
Karolinska Institute, Department of Biosciences/Department of Natural Sciences, University College Sodertorn Alfred Nobel's Alle 7, S-141 89, Huddinge, Sweden.
Nucleic Acids Res. 2005 May 20;33(9):2868-79. doi: 10.1093/nar/gki579. Print 2005.
Centromeres of fission yeast are arranged with a central core DNA sequence flanked by repeated sequences. The centromere-associated histone H3 variant Cnp1 (SpCENP-A) binds exclusively to central core DNA, while the heterochromatin proteins and cohesins bind the surrounding outer repeats. CHD (chromo-helicase/ATPase DNA binding) chromatin remodeling factors were recently shown to affect chromatin assembly in vitro. Here, we report that the CHD protein Hrp1 plays a key role at fission yeast centromeres. The hrp1Delta mutant disrupts silencing of the outer repeats and central core regions of the centromere and displays chromosome segregation defects characteristic for dysfunction of both regions. Importantly, Hrp1 is required to maintain high levels of Cnp1 and low levels of histone H3 and H4 acetylation at the central core region. Hrp1 interacts directly with the centromere in early S-phase when centromeres are replicated, suggesting that Hrp1 plays a direct role in chromatin assembly during DNA replication.
裂殖酵母的着丝粒由一个中央核心DNA序列和两侧的重复序列组成。着丝粒相关组蛋白H3变体Cnp1（SpCENP-A）仅与中央核心DNA结合，而异染色质蛋白和黏连蛋白则结合周围的外侧重复序列。最近研究表明，CHD（染色质解旋酶/ATP酶DNA结合）染色质重塑因子在体外会影响染色质组装。在此，我们报告CHD蛋白Hrp1在裂殖酵母着丝粒中起关键作用。hrp1Δ突变体破坏了着丝粒外侧重复序列和中央核心区域的沉默，并表现出这两个区域功能障碍所特有的染色体分离缺陷。重要的是，维持中央核心区域高水平的Cnp1以及低水平的组蛋白H3和H4乙酰化需要Hrp1。在着丝粒复制的S期早期，Hrp1直接与着丝粒相互作用，这表明Hrp1在DNA复制过程中的染色质组装中起直接作用。
