Xu Heng-hao, Su Trent, Xue Yong
Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Huaihai Institute of Technology, Lianyungang 222005, China.
Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Lianyungang, 222005, China.
Sci Rep. 2016 Feb 24;6:21900. doi: 10.1038/srep21900.
Histone variants and histone modifications are essential components in the establishment and maintenance of the repressed status of heterochromatin. Among these histone variants and modifications, acetylation at histone H4K16 is uniquely important for the maintenance of silencing at telomere and mating type loci but not at the ribosomal DNA locus. Here we show that mutations at H3 N-terminal acetylation site K14 specifically disrupt rDNA silencing. However, the mutant ion at H3K14R doesn't affect the recruitment of Pol II repressor RENT (regulator of nucleolar silencing and telophase exit) complex at the rDNA region. Instead, the CAF-1(chromatin assembly factor I) subunit Cac2 level decreased in the H3K14R mutant. Further experiments revealed that the single mutation at H3K14 and multi-site mutations at H3 N-terminus including K14 also delayed replication-depend nucleosome assembly and advanced replicative life span. In conclusion, our data suggest that histone H3 N-terminal acetylation sites especially at K14 are important for rDNA silencing and aging.
组蛋白变体和组蛋白修饰是异染色质抑制状态建立和维持的重要组成部分。在这些组蛋白变体和修饰中，组蛋白H4K16位点的乙酰化对于端粒和交配型位点沉默的维持尤为重要，但对核糖体DNA位点的沉默维持并非如此。在此我们表明，H3 N端乙酰化位点K14的突变特异性地破坏了核糖体DNA沉默。然而，H3K14R突变体并不影响Pol II阻遏物RENT（核仁沉默和末期退出调节因子）复合物在核糖体DNA区域的募集。相反，H3K14R突变体中CAF-1（染色质组装因子I）亚基Cac2的水平降低。进一步的实验表明，H3K14的单突变以及H3 N端包括K14在内的多位点突变也延迟了复制依赖性核小体组装并延长了复制寿命。总之，我们的数据表明组蛋白H3 N端乙酰化位点尤其是K14位点对于核糖体DNA沉默和衰老很重要。
