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Epitranscriptomics & Cancer Adaptation : A.David

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Our research work focuses on the contribution of post-transcriptional mechanisms on cancer cell adaptation, in particular RNA epigenetic & translational control.

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Group name EquipeCTCS
Item Type Journal Article
Title PRMT5-mediated histone H4 arginine-3 symmetrical dimethylation marks chromatin at G + C-rich regions of the mouse genome
Creator Girardot et al.
Author Michael Girardot
Author Ryutaro Hirasawa
Author Salim Kacem
Author Lauriane Fritsch
Author Julien Pontis
Author Satya K. Kota
Author Doria Filipponi
Author Eric Fabbrizio
Author Claude Sardet
Author Felix Lohmann
Author Shilpa Kadam
Author Slimane Ait-Si-Ali
Author Robert Feil
Abstract Symmetrical dimethylation on arginine-3 of histone H4 (H4R3me2s) has been reported to occur at several repressed genes, but its specific regulation and genomic distribution remained unclear. Here, we show that the type-II protein arginine methyltransferase PRMT5 controls H4R3me2s in mouse embryonic fibroblasts (MEFs). In these differentiated cells, we find that the genome-wide pattern of H4R3me2s is highly similar to that in embryonic stem cells. In both the cell types, H4R3me2s peaks are detected predominantly at G + C-rich regions. Promoters are consistently marked by H4R3me2s, independently of transcriptional activity. Remarkably, H4R3me2s is mono-allelic at imprinting control regions (ICRs), at which it marks the same parental allele as H3K9me3, H4K20me3 and DNA methylation. These repressive chromatin modifications are regulated independently, however, since PRMT5-depletion in MEFs resulted in loss of H4R3me2s, without affecting H3K9me3, H4K20me3 or DNA methylation. Conversely, depletion of ESET (KMT1E) or SUV420H1/H2 (KMT5B/C) affected H3K9me3 and H4K20me3, respectively, without altering H4R3me2s at ICRs. Combined, our data indicate that PRMT5-mediated H4R3me2s uniquely marks the mammalian genome, mostly at G + C-rich regions, and independently from transcriptional activity or chromatin repression. Furthermore, comparative bioinformatics analyses suggest a putative role of PRMT5-mediated H4R3me2s in chromatin configuration in the nucleus.
Publication Nucleic Acids Research
Volume 42
Issue 1
Pages 235-248
Date Jan 2014
Journal Abbr Nucleic Acids Res.
Language eng
DOI 10.1093/nar/gkt884
ISSN 1362-4962
Library Catalog PubMed
Extra PMID: 24097435 PMCID: PMC3874197
Tags Alleles, Animals, Arginine, Cells, Cultured, Chromatin, DNA Methylation, Fibroblasts, GC Rich Sequence, Genomic Imprinting, Histones, Methylation, Mice, original, Promoter Regions, Genetic, Protein Methyltransferases, Protein-Arginine N-Methyltransferases
Date Added 2019/05/31 - 11:47:28
Date Modified 2019/05/31 - 11:47:57
Notes and Attachments PubMed entry (Attachment)
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