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.
PRMT5-mediated histone H4 arginine-3 symmetrical dimethylation marks chromatin at G + C-rich regions of the mouse genome
Girardot§, M.; Hirasawa§, R.; Kacem, S.; Fritsch, L.; Pontis, J.; Kota, S. K.; Filipponi, D.; Fabbrizio, E.; Sardet, C.; Lohmann, F.; Kadam, S.; Ait-Si-Ali, S.; Feil, R.
Nucleic Acids Res
2014-01 / vol 42 / pages 235-48
10.1093/nar/gkt884 gkt884 [pii]
1362-4962 (Electronic) 0305-1048 (Linking)
IGMM team(s) involved in this publication
Genomic Imprinting and Development
Animals; Cells, Cultured; Mice; DNA Methylation; Alleles; Genomic Imprinting; Methylation; Genome; *GC Rich Sequence; Arginine/*metabolism; Chromatin/*enzymology; Fibroblasts/enzymology; Histones/chemistry/*metabolism; Promoter Regions, Genetic; Protein Methyltransferases/*metabolism