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Open AccessArticle

The H3K9 Methylation Writer SETDB1 and its Reader MPP8 Cooperate to Silence Satellite DNA Repeats in Mouse Embryonic Stem Cells

1
Epigenetics and Cell Fate (EDC), Centre National de la Recherche Scientifique (CNRS), Université de Paris, Université Paris Diderot, F-75013, Paris, France
2
Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 111221, Colombia
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School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, Colombia
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Doctoral Program in Biomedical and Biological Sciences, Universidad del Rosario, Bogotá 111221, Colombia
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Current: Ecole Polytechnique Fédérale de Lausanne (EPFL); SV LVG Station 19, 1015 Lausanne, Switzerland
*
Author to whom correspondence should be addressed.
Genes 2019, 10(10), 750; https://doi.org/10.3390/genes10100750
Received: 25 August 2019 / Revised: 15 September 2019 / Accepted: 24 September 2019 / Published: 25 September 2019
(This article belongs to the Special Issue Transcriptional Regulation of Early Embryogenesis)
SETDB1 (SET Domain Bifurcated histone lysine methyltransferase 1) is a key lysine methyltransferase (KMT) required in embryonic stem cells (ESCs), where it silences transposable elements and DNA repeats via histone H3 lysine 9 tri-methylation (H3K9me3), independently of DNA methylation. The H3K9 methylation reader M-Phase Phosphoprotein 8 (MPP8) is highly expressed in ESCs and germline cells. Although evidence of a cooperation between H3K9 KMTs and MPP8 in committed cells has emerged, the interplay between H3K9 methylation writers and MPP8 in ESCs remains elusive. Here, we show that MPP8 interacts physically and functionally with SETDB1 in ESCs. Indeed, combining biochemical, transcriptomic and genomic analyses, we found that MPP8 and SETDB1 co-regulate a significant number of common genomic targets, especially the DNA satellite repeats. Together, our data point to a model in which the silencing of a class of repeated sequences in ESCs involves the cooperation between the H3K9 methylation writer SETDB1 and its reader MPP8. View Full-Text
Keywords: M-Phase Phosphoprotein 8, SETDB1/KMT1E; histone lysine methylation, satellite DNA repeats, transcription M-Phase Phosphoprotein 8, SETDB1/KMT1E; histone lysine methylation, satellite DNA repeats, transcription
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Cruz-Tapias, P.; Robin, P.; Pontis, J.; Maestro, L.D.; Ait-Si-Ali, S. The H3K9 Methylation Writer SETDB1 and its Reader MPP8 Cooperate to Silence Satellite DNA Repeats in Mouse Embryonic Stem Cells. Genes 2019, 10, 750.

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