The profile of repeat-associated histone lysine methylation states in the mouse epigenome

The profile of repeat-associated histone lysine methylation states in the mouse epigenome
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DOI:
10.1038/sj.emboj.7600545
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发表时间:
2005-02-23
期刊:
影响因子:
11.4
通讯作者:
Jenuwein, T
Jenuwein, T
中科院分区:
生物学1区
文献类型:
--
作者:
Martens, JHA;O'Sullivan, RJ;Jenuwein, T

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组蛋白赖氨酸甲基化已被证明可标记沉默的染色质区域,例如在着丝粒周围异染色质或失活的X染色体上。在此,我们研究了抑制性组蛋白赖氨酸甲基化状态在小鼠基因组中整个DNA重复序列家族中的分布。通过对代表重复元件的聚类分析进行染色质免疫沉淀,我们的数据表明,不同的H3 - K9、H3 - K27和H4 - K20甲基化标记在串联重复序列(例如大卫星和小卫星)、DNA转座子、反转录转座子、长散在核元件和短散在核元件中存在选择性富集。串联重复序列(而非其他重复元件)会产生双链(ds)RNA,在缺乏H3 - K9特异性Suv39h组蛋白甲基转移酶的胚胎干细胞(ES)中,这种RNA进一步增加。重要的是,尽管H3 - K9三甲基化和H4 - K20三甲基化在卫星重复序列处似乎稳定,但许多其他与重复相关的抑制性标记在分化的ES细胞或胚胎滋养层细胞和成纤维细胞的染色质中有所不同。我们的数据确定了四种不同小鼠表观基因组重复部分的抑制性组蛋白赖氨酸甲基化状态图谱,并表明串联重复序列和dsRNA是更稳定的染色质印记的主要触发因素。
Histone lysine methylation has been shown to index silenced chromatin regions at, for example, pericentric heterochromatin or of the inactive X chromosome. Here, we examined the distribution of repressive histone lysine methylation states over the entire family of DNA repeats in the mouse genome. Using chromatin immunoprecipitation in a cluster analysis representing repetitive elements, our data demonstrate the selective enrichment of distinct H3- K9, H3- K27 and H4- K20 methylation marks across tandem repeats ( e. g. major and minor satellites), DNA transposons, retrotransposons, long interspersed nucleotide elements and short interspersed nucleotide elements. Tandem repeats, but not the other repetitive elements, give rise to double- stranded ( ds) RNAs that are further elevated in embryonic stem ( ES) cells lacking the H3- K9-specific Suv39h histone methyltransferases. Importantly, although H3- K9 tri- and H4- K20 trimethylation appear stable at the satellite repeats, many of the other repeat-associated repressive marks vary in chromatin of differentiated ES cells or of embryonic trophoblasts and fibroblasts. Our data define a profile of repressive histone lysine methylation states for the repetitive complement of four distinct mouse epigenomes and suggest tandem repeats and dsRNA as primary triggers for more stable chromatin imprints.