Gómez Eliana B, Espinosa Joaquín M, Forsburg Susan L
Molecular & Computational Biology Section, University of Southern California, Los Angeles, 90089-2910, USA.
Mol Cell Biol. 2005 Oct;25(20):8887-903. doi: 10.1128/MCB.25.20.8887-8903.2005.
Histone acetylation and deacetylation are associated with transcriptional activity and the formation of constitutively silent heterochromatin. Increasingly, histone acetylation is also implicated in other chromosome transactions, including replication and segregation. We have cloned the only Schizosaccharomyces pombe MYST family histone acetyltransferase genes, mst1(+) and mst2(+). Mst1p, but not Mst2p, is essential for viability. Both proteins are localized to the nucleus and bound to chromatin throughout the cell cycle. Deltamst2 genetically interacts with mutants that affect heterochromatin, cohesion, and telomere structure. Mst2p is a negative regulator of silencing at the telomere but does not affect silencing in the centromere or mating type region. We generated a census of proteins and histone modifications at wild-type telomeres. A histone acetylation gradient at the telomeres is lost in Deltamst2 cells without affecting the distribution of Taz1p, Swi6p, Rad21p, or Sir2p. We propose that the increased telomeric silencing is caused by histone hypoacetylation and/or an increase in the ratio of methylated to acetylated histones. Although telomere length is normal, meiosis is aberrant in Deltamst2 diploid homozygote mutants, suggesting that telomeric histone acetylation contributes to normal meiotic progression.
组蛋白乙酰化和去乙酰化与转录活性以及组成型沉默异染色质的形成有关。越来越多的研究表明，组蛋白乙酰化还参与其他染色体活动，包括复制和分离。我们克隆了粟酒裂殖酵母中唯一的MYST家族组蛋白乙酰转移酶基因mst1(+)和mst2(+)。Mst1p对细胞存活至关重要，而Mst2p并非如此。这两种蛋白都定位于细胞核，并在整个细胞周期中与染色质结合。Deltamst2与影响异染色质、黏连蛋白和端粒结构的突变体存在遗传相互作用。Mst2p是端粒沉默的负调控因子，但不影响着丝粒或交配型区域的沉默。我们对野生型端粒处的蛋白质和组蛋白修饰进行了普查。在Deltamst2细胞中，端粒处的组蛋白乙酰化梯度消失，但不影响Taz1p、Swi6p、Rad21p或Sir2p的分布。我们认为，端粒沉默增强是由组蛋白低乙酰化和/或甲基化与乙酰化组蛋白比例增加所致。尽管端粒长度正常，但Deltamst2二倍体纯合突变体的减数分裂异常，这表明端粒组蛋白乙酰化有助于正常的减数分裂进程。
