The FUN30 Chromatin Remodeler, Fft3, Protects Centromeric and Subtelomeric Domains from Euchromatin Formation

The chromosomes of eukaryotes are organized into structurally and functionally discrete domains. This implies the presence of insulator elements that separate adjacent domains, allowing them to maintain different chromatin structures. We show that the Fun30 chromatin remodeler, Fft3, is essential for maintaining a proper chromatin structure at centromeres and subtelomeres. Fft3 is localized to insulator elements and inhibits euchromatin assembly in silent chromatin domains. In its absence, euchromatic histone modifications and histone variants invade centromeres and subtelomeres, causing a mis-regulation of gene expression and severe chromosome segregation defects. Our data strongly suggest that Fft3 controls the identity of chromatin domains by protecting these regions from euchromatin assembly.真核生物的染色体被组织为结构与功能上均相互独立的结构域。这意味着存在能够分隔相邻结构域的绝缘子元件（insulator elements），使各结构域得以维持不同的染色质结构。本研究表明，Fun30染色质重塑因子（Fun30 chromatin remodeler）Fft3对于维持着丝粒与亚端粒区域的正常染色质结构至关重要。Fft3定位于绝缘子元件，并可在沉默染色质结构域中抑制常染色质的组装。当Fft3缺失时，常染色质型组蛋白修饰与组蛋白变体便会侵入着丝粒与亚端粒区域，导致基因表达调控失常以及严重的染色体分离缺陷。本研究数据强有力地表明，Fft3通过保护上述区域免受常染色质组装的影响，从而调控染色质结构域的特性。