PRMT5-mediated histone H4 arginine-3 symmetrical dimethylation marks chromatin at G + C-rich regions of the mouse genome.

PRMT5-mediated histone H4 arginine-3 symmetrical dimethylation marks chromatin at G + C-rich regions of the mouse genome.
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DOI:
10.1093/nar/gkt884
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发表时间:
2014-01
影响因子:
14.9
通讯作者:
Feil R
Feil R
中科院分区:
生物学2区
文献类型:
--
作者:
Girardot M;Hirasawa R;Kacem S;Fritsch L;Pontis J;Kota SK;Filipponi D;Fabbrizio E;Sardet C;Lohmann F;Kadam S;Ait-Si-Ali S;Feil R

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组蛋白H4精氨酸3位对称二甲基化(H4 R3 me 2s)已被报道发生在几个受抑制基因上,但其具体调控和基因组分布尚不清楚。在这里,我们表明,II型蛋白质精氨酸甲基转移酶PRMT 5控制H4 R3 me 2s在小鼠胚胎成纤维细胞(MEFs)。在这些分化的细胞中,我们发现H4 R3 me 2s的全基因组模式与胚胎干细胞中的模式高度相似。在这两种细胞类型中,H4 R3 me 2s峰主要在富含G + C的区域检测到。启动子一致地由H4 R3 me 2s标记,独立于转录活性。值得注意的是,H4 R3 me 2s在印记控制区(ICR)是单等位基因,在那里它标记与H3 K9 me 3,H4 K20 me 3和DNA甲基化相同的亲本等位基因。然而,这些抑制性染色质修饰是独立调节的,因为MEFs中的PRMT 5缺失导致H4 R3 me 2s的丢失,而不影响H3 K9 me 3、H4 K20 me 3或DNA甲基化。相反,ESET(KMT 1 E)或SUV 420 H1/H2(KMT 5 B/C)的耗竭分别影响H3 K9 me 3和H4 K20 me 3,而不改变ICR处的H4 R3 me 2。结合,我们的数据表明,PRMT 5介导的H4 R3 me 2s独特地标志着哺乳动物基因组,主要是在G + C丰富的区域,并独立于转录活性或染色质抑制。此外,比较生物信息学分析表明PRMT 5介导的H4 R3 me 2s在细胞核中的染色质构型中的假定作用。
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.
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发表时间: 2006-06-01
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