Laboratory Thomas Jenuwein

Genome-wide signatures for heterochromatin

Interstitial heterochromatin is required to restrict aberrant expression of retrotransposons, but it remains poorly defined due to the underlying repeat-rich sequences. We dissected Suv39h-dependent histone H3 lysine 9 trimethylation (H3K9me3) by genome-wide ChIP-sequencing in mouse embryonic stem cells (ESCs) (Bulut-Karslioglu et al., submitted).

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Suv39h enzymes target retrotransposons in mouse ESCs; ChIP-seq analysis for H3K9me3 in wild-type and Suv39h dn embryonic stem cells (ESCs) and for Suv39h enzymes in Suv39h1- and Suv39h2-HA/FLAG knock-in ESCs. A representative region of 30 kb on chromosome 11, which contains several LINE and LTR elements, is shown. [less]

Refined bioinformatic analyses of repeat subfamilies indicated selective accumulation of Suv39h-dependent H3K9me3 at interspersed repetitive elements that cover ~ 5% of the ESC epigenome. The majority of the ~ 8,150 intact long interspersed nuclear elements (LINEs) and endogenous retroviruses (ERVs), but only a minor fraction of the > 1.8 million degenerate and truncated LINEs/ERVs, are enriched for Suv39h-dependent H3K9me3. Transcriptional repression of these intact LINEs and ERVs is differentially regulated by Suv39h and other chromatin modifiers in ESCs but governed by DNA methylation in committed cells. These data provide a novel function for Suv39h-dependent H3K9me3 chromatin in the ESC epigenome and reveal that interstitial heterochromatin is restricted to the intact fraction of retrotransposon elements.

We plan to extend our genome-wide analyses to other core components of heterochromatin and to identify non-coding RNA moieties that associate with these factors.