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DOI | 10.1002/2016WR019191 |
Intragenic DNA methylation prevents spurious transcription initiation | |
Neri, Francesco1,2; Rapelli, Stefania3; Krepelova, Anna1,3; Incarnato, Danny1; Parlato, Caterina1; Basile, Giulia1; Maldotti, Mara1,3; Anselmi, Francesca1,3; Oliviero, Salvatore1,3 | |
2017-03-02 | |
发表期刊 | NATURE
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ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2017 |
卷号 | 543期号:7643页码:72-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Italy; Germany |
英文摘要 | In mammals, DNA methylation occurs mainly at CpG dinucleotides. Methylation of the promoter suppresses gene expression, but the functional role of gene-body DNA methylation in highly expressed genes has yet to be clarified. Here we show that, in mouse embryonic stem cells, Dnmt3b-dependent intragenic DNA methylation protects the gene body from spurious RNA polymerase II entry and cryptic transcription initiation. Using different genome-wide approaches, we demonstrate that this Dnmt3b function is dependent on its enzymatic activity and recruitment to the gene body by H3K36me3. Furthermore, the spurious transcripts can either be degraded by the RNA exosome complex or capped, polyadenylated, and delivered to the ribosome to produce aberrant proteins. Elongating RNA polymerase II therefore triggers an epigenetic crosstalk mechanism that involves SetD2, H3K36me3, Dnmt3b and DNA methylation to ensure the fidelity of gene transcription initiation, with implications for intragenic hypomethylation in cancer. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000395671500034 |
WOS关键词 | GENOME-WIDE ANALYSIS ; RNA-POLYMERASE-II ; METHYLTRANSFERASES DNMT3A ; TUMOR-SUPPRESSOR ; SP1 BINDING ; HALF-LIFE ; GENE ; STEM ; REVEALS ; SETD2 |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/21399 |
专题 | 资源环境科学 |
作者单位 | 1.Human Genet Fdn HuGeF, Via Nizza 52, I-10126 Turin, Italy; 2.Leibniz Inst Aging FLI, Beutenbergstr 11, D-07745 Jena, Germany; 3.Univ Torino, Dipartimento Sci Vita & Biol Sistemi, Via Accademia Albertina 13, I-10123 Turin, Italy |
推荐引用方式 GB/T 7714 | Neri, Francesco,Rapelli, Stefania,Krepelova, Anna,et al. Intragenic DNA methylation prevents spurious transcription initiation[J]. NATURE,2017,543(7643):72-+. |
APA | Neri, Francesco.,Rapelli, Stefania.,Krepelova, Anna.,Incarnato, Danny.,Parlato, Caterina.,...&Oliviero, Salvatore.(2017).Intragenic DNA methylation prevents spurious transcription initiation.NATURE,543(7643),72-+. |
MLA | Neri, Francesco,et al."Intragenic DNA methylation prevents spurious transcription initiation".NATURE 543.7643(2017):72-+. |
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