Molecular Cell

Molecular Cell

Volume 55, Issue 2, 17 July 2014, Pages 277-290
Journal home page for Molecular Cell

Article
Suv39h-Dependent H3K9me3 Marks Intact Retrotransposons and Silences LINE Elements in Mouse Embryonic Stem Cells

https://doi.org/10.1016/j.molcel.2014.05.029Get rights and content
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Highlights

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    Comprehensive genome-wide analysis of Suv39h-dependent H3K9me3 in mouse ESCs

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    Role for Suv39h KMTs in depositing H3K9me3 at intact ERVs and LINEs

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    Suv39h KMTs specifically silence LINE1/L1Md A elements in mouse ESCs

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    Dynamic distribution of Suv39h-dependent H3K9me3 in ESCs versus committed cells

Summary

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). 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 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 function for Suv39h-dependent H3K9me3 chromatin to specifically repress intact LINE elements in the ESC epigenome.

Cited by (0)

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Present address: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Obstetrics and Gynecology and Center for Reproductive Sciences, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA

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Present address: Department of Medicine II, Klinikum Rechts der Isar, Technische Universität München, 81675 München, Germany

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Present address: Department of Pediatrics, Stanford University, Stanford, CA 94305, USA

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Present address: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA

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Present address: Department of Genetics, Evolution, and Environment, UCL Genetics Institute, Gower Street, University College, London WC1E 6BT, UK

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Present address: Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213-1863, USA

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Present address: Radboud University, Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, 6500 HB Nijmegen, The Netherlands

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Co-first authors

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