Ragunathan Kaushik, Jih Gloria, Moazed Danesh
Department of Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Science. 2015 Apr 3;348(6230):1258699. doi: 10.1126/science.1258699. Epub 2014 Nov 20.
Changes in histone posttranslational modifications are associated with epigenetic states that define distinct patterns of gene expression. It remains unclear whether epigenetic information can be transmitted through histone modifications independently of specific DNA sequence, DNA methylation, or RNA interference. Here we show that, in the fission yeast Schizosaccharomyces pombe, ectopically induced domains of histone H3 lysine 9 methylation (H3K9me), a conserved marker of heterochromatin, are inherited through several mitotic and meiotic cell divisions after removal of the sequence-specific initiator. The putative JmjC domain H3K9 demethylase, Epe1, and the chromodomain of the H3K9 methyltransferase, Clr4/Suv39h, play opposing roles in maintaining silent H3K9me domains. These results demonstrate how a direct "read-write" mechanism involving Clr4 propagates histone modifications and allows histones to act as carriers of epigenetic information.
组蛋白翻译后修饰的变化与定义不同基因表达模式的表观遗传状态相关。目前尚不清楚表观遗传信息是否可以通过组蛋白修饰独立于特定DNA序列、DNA甲基化或RNA干扰进行传递。在这里,我们表明,在裂殖酵母粟酒裂殖酵母中,组蛋白H3赖氨酸9甲基化(H3K9me)的异位诱导结构域是一种异染色质的保守标记,在去除序列特异性启动子后,通过几次有丝分裂和减数分裂细胞分裂得以遗传。推定的JmjC结构域H3K9去甲基化酶Epe1和H3K9甲基转移酶Clr4/Suv39h的色域在维持沉默的H3K9me结构域中发挥相反作用。这些结果证明了涉及Clr4的直接“读写”机制如何传播组蛋白修饰,并使组蛋白能够作为表观遗传信息的载体。