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

• Published in: Molecular cell Vol. 55; no. 2; pp. 277 - 290
• Main Authors: Bulut-Karslioglu, Aydan, De La Rosa-Velázquez, Inti A., Ramirez, Fidel, Barenboim, Maxim, Onishi-Seebacher, Megumi, Arand, Julia, Galán, Carmen, Winter, Georg E., Engist, Bettina, Gerle, Borbala, O’Sullivan, Roderick J., Martens, Joost H.A., Walter, Jörn, Manke, Thomas, Lachner, Monika, Jenuwein, Thomas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.07.2014
• Subjects: Animals; bioinformatics; Cells, Cultured; DNA Methylation; embryonic stem cells; Embryonic Stem Cells - enzymology; Endogenous Retroviruses - genetics; Gene Silencing; heterochromatin; Histone-Lysine N-Methyltransferase - physiology; histones; Histones - metabolism; Long Interspersed Nucleotide Elements; lysine; Methyltransferases - physiology; Mice; Protein Processing, Post-Translational; Repressor Proteins - physiology; retrotransposons; Retroviridae; Retrovirus; transcription (genetics)
• ISSN: 1097-2765; 1097-4164; 1097-4164
• DOI: 10.1016/j.molcel.2014.05.029

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. [Display omitted] •Comprehensive genome-wide analysis of Suv39h-dependent H3K9me3 in mouse ESCs•Role for Suv39h KMTs in depositing H3K9me3 at intact ERVs and LINEs•Suv39h KMTs specifically silence LINE1/L1Md A elements in mouse ESCs•Dynamic distribution of Suv39h-dependent H3K9me3 in ESCs versus committed cells Suv39h-dependent H3K9me3 is crucial for pericentric heterochromatin formation in mammals; however, its genome-wide function remains unknown. Bulut-Karslioglu et al. show that Suv39h enzymes target intact retrotransposons in mouse ESCs and are specifically required to silence LINE1 elements. These data extend the role of Suv39h KMTs in safeguarding genome integrity.