DNMT1-interacting RNAs block gene-specific DNA methylation

被引：399

作者：

Di Ruscio, Annalisa ^{[1
,2
]}

Ebralidze, Alexander K. ^{[1
,2
]}

Benoukraf, Touati ^{[4
]}

Amabile, Giovanni ^{[1
,2
]}

Goff, Loyal A. ^{[5
,6
,7
]}

Terragni, Jolyon ^{[8
]}

Figueroa, Maria Eugenia ^{[9
]}

Pontes, Lorena Lobo De Figueiredo ^{[1
,2
]}

Alberich-Jorda, Meritxell ^{[1
,2
,10
]}

Zhang, Pu ^{[1
]}

Wu, Mengchu ^{[4
]}

D'Alo, Francesco ^{[3
]}

Melnick, Ari ^{[11
]}

Leone, Giuseppe ^{[3
]}

Ebralidze, Konstantin K. ^{[2
]}

Pradhan, Sriharsa ^{[8
]}

Rinn, John L. ^{[1
,2
,5
,6
]}

Tenen, Daniel G. ^{[1
,4
]}

机构：

[1] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA

[2] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

[3] Univ Cattolica Sacro Cuore, Inst Hematol, I-00168 Rome, Italy

[4] Natl Univ Singapore, Canc Sci Inst, Singapore 117599, Singapore

[5] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[6] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA

[7] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA

[8] New England Biolabs Inc, Ipswich, MA 01938 USA

[9] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[10] Acad Sci Czech Republ, Inst Mol Genet, CR-14220 Prague, Czech Republic

[11] C620 Weill Cornell Med Coll, Dept Med, New York, NY 10021 USA

来源：

NATURE | 2013年 / 503卷 / 7476期

基金：

美国国家卫生研究院; 巴西圣保罗研究基金会; 英国医学研究理事会; 新加坡国家研究基金会;

关键词：

GENOME-WIDE IDENTIFICATION; TRANSCRIPTION FACTORS; EXPRESSION; MAINTENANCE; POLYMERASE; METHYLTRANSFERASE; CHROMATIN; REVEALS; CANCER; SITES;

D O I：

10.1038/nature12598

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

DNA methylation was first described almost a century ago; however, the rules governing its establishment and maintenance remain elusive. Here we present data demonstrating that active transcription regulates levels of genomic methylation. We identify a novel RNA arising from the CEBPA gene locus that is critical in regulating the local DNA methylation profile. This RNA binds to DNMT1 and prevents CEBPA gene locus methylation. Deep sequencing of transcripts associated with DNMT1 combined with genome-scale methylation and expression profiling extend the generality of this finding to numerous gene loci. Collectively, these results delineate the nature of DNMT1-RNA interactions and suggest strategies for gene-selective demethylation of therapeutic targets in human diseases.

引用

页码：371 / +

页数：10

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