Ekwall K, Olsson T, Turner B M, Cranston G, Allshire R C
MRC Human Genetics Unit, Western General Hospital, Edinburgh, Scotland, United Kingdom.
Cell. 1997 Dec 26;91(7):1021-32. doi: 10.1016/s0092-8674(00)80492-4.
Histone acetylation may act to mark and maintain transcriptionally active or inactive chromosomal domains through the cell cycle and in different lineages. A novel role for histone acetylation in centromere regulation has been identified. Exposure of fission yeast cells to TSA, a specific inhibitor of histone deacetylase, interferes with repression of marker genes in centromeric heterochromatin, causes chromosome loss, and disrupts the localization of Swi6p, a component of centromeric heterochromatin. Transient TSA treatment induces a heritable hyperacetylated state in centromeric chromatin that is propagated in lineages in the absence of drug. This state is linked in cis to the treated centromere locus and correlates with inheritance of functionally defective centromeres and persistent chromosome segregation problems. Thus, assembly of fully functional centromeres is partly imprinted in the underacetylated or transcriptionally silent state of centromeric chromatin.
组蛋白乙酰化可能通过细胞周期并在不同谱系中标记和维持转录活性或非活性染色体结构域。已确定组蛋白乙酰化在着丝粒调控中具有新作用。将裂殖酵母细胞暴露于曲古抑菌素A(TSA,一种组蛋白脱乙酰酶的特异性抑制剂)会干扰着丝粒异染色质中标记基因的抑制,导致染色体丢失,并破坏着丝粒异染色质成分Swi6p的定位。短暂的TSA处理会在着丝粒染色质中诱导一种可遗传的超乙酰化状态,这种状态在无药物的谱系中得以延续。这种状态在顺式中与经处理的着丝粒位点相关联,并与功能缺陷着丝粒的遗传以及持续的染色体分离问题相关。因此,功能完全正常的着丝粒的组装部分地印记在着丝粒染色质的低乙酰化或转录沉默状态中。