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

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.

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