Group Leader

Prof. Dr. Thomas Jenuwein
Prof. Dr. Thomas Jenuwein
Senior Group Leader & Director
Phone:+49 761 5108-785

Lab Thomas Jenuwein

Assistant: Marcela Mare Phone: +49 761 5108 574 Email: mare@ie-freiburg.mpg.de

Laboratory Thomas Jenuwein

How to make 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 H3K9me3 by genome-wide ChIP-sequencing in mouse embryonic stem cells (ESCs) (Bulut-Karslioglu et al., submitted).

Model for the distinction between euchromatin and heterochromatin that is based on a synergistic vs. a more random organization of transcription factor binding sites. TF: transcription factor; KMT/Suv39h: histone methyltransferase; HP1: Heterochromatic Protein 1. Zoom Image
Model for the distinction between euchromatin and heterochromatin that is based on a synergistic vs. a more random organization of transcription factor binding sites. TF: transcription factor; KMT/Suv39h: histone methyltransferase; HP1: Heterochromatic Protein 1. [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.

 
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