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The H3K9 methylation writer SETDB1 and its reader MPP8 cooperate to silence satellite DNA repeats in mouse embryonic stem cells
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Cruz-Tapias, Paola
Robin, Philippe
Pontis, Julien
Del Maestro, Laurence
Ait-Si-Ali, Slimane
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Fecha
2019
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MDPI AG
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Resumen
Abstract
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. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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Keywords
Histone H3 , Cultured , M phase phosphoprotein 8 , Phosphoprotein , Repetitive DNA , Satellite DNA , SET domain bifurcated histone lysine methyltransferase 1 , Small interfering RNA , Unclassified drug , Histone , Histone lysine methyltransferase , Mphosph8 protein , Phosphoprotein , Protein binding , Satellite DNA , SETDB1 protein , Animal cell , Article , Binding site , Biochemical analysis , Cell cycle M phase , Chromatin immunoprecipitation , Comparative study , Complex formation , Controlled study , Down regulation , Embryo , Gene , Gene control , Gene expression , Gene expression regulation , Gene function , Gene number , Gene silencing , Gene targeting , Genomics , Hela S3 cell line , Histone methylation , Immunoprecipitation , Long interspersed nuclear element , Loss of function mutation , Molecular genetics , Mouse , Mouse embryonic stem cell , MPP8 gene , Nonhuman , Protein processing , Protein protein interaction , RNA sequence , SETDB1 gene , Short interspersed nuclear element , Transcriptomics , Upregulation , Animal , Cell culture , Genetics , Hela cell line , Human , Metabolism , Mouse embryonic stem cell , Animals , Cells , DNA , Hela Cells , Histone-Lysine N-Methyltransferase , Histones , Humans , Mice , Mouse Embryonic Stem Cells , Phosphoproteins , Protein Binding , Histone lysine methylation , M-phase phosphoprotein 8 , Satellite DNA repeats , SETDB1/KMT1E , Transcription
