title: MicroRNAs activate gene transcription epigenetically as an enhancer trigger.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that function as negative gene expression regulators. Emerging evidence shows that, except for function in the cytoplasm, miRNAs are also present in the nucleus. However, the functional significance of nuclear miRNAs remains largely undetermined. By screening miRNA database, we have identified a subset of miRNA that functions as enhancer regulators. Here, we found a set of miRNAs show gene-activation function. We focused on miR-24-1 and found that this miRNA unconventionally activates gene transcription by targeting enhancers. Consistently, the activation was completely abolished when the enhancer sequence was deleted by TALEN. Furthermore, we found that miR-24-1 activates enhancer RNA (eRNA) expression, alters histone modification, and increases the enrichment of p300 and RNA Pol II at the enhancer locus. Our results demonstrate a novel mechanism of miRNA as an enhancer trigger.
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|b Key Laboratory of Ministry of Education , Department of Molecular Biology, Fudan University , Shanghai , China.|c Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University , Shanghai , China.
authors: Min
authors: M
authors: Xiao
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|b Key Laboratory of Ministry of Education , Department of Molecular Biology, Fudan University , Shanghai , China.|c Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University , Shanghai , China.
authors: Jin
authors: J
authors: Li
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|b Key Laboratory of Ministry of Education , Department of Molecular Biology, Fudan University , Shanghai , China.|c Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University , Shanghai , China.
authors: Wei
authors: W
authors: Li
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|b Key Laboratory of Ministry of Education , Department of Molecular Biology, Fudan University , Shanghai , China.
authors: Yu
authors: Y
authors: Wang
authors: d Laboratory of Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.
authors: Feizhen
authors: F
authors: Wu
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|b Key Laboratory of Ministry of Education , Department of Molecular Biology, Fudan University , Shanghai , China.
authors: Yanping
authors: Y
authors: Xi
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|b Key Laboratory of Ministry of Education , Department of Molecular Biology, Fudan University , Shanghai , China.
authors: Lan
authors: L
authors: Zhang
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|e The Experimental Training Center for Basic Medical Sciences, The Second Military Medical University , Shanghai , China.
authors: Chao
authors: C
authors: Ding
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|b Key Laboratory of Ministry of Education , Department of Molecular Biology, Fudan University , Shanghai , China.
authors: Huaibing
authors: H
authors: Luo
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|b Key Laboratory of Ministry of Education , Department of Molecular Biology, Fudan University , Shanghai , China.
authors: Yan
authors: Y
authors: Li
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|b Key Laboratory of Ministry of Education , Department of Molecular Biology, Fudan University , Shanghai , China.
authors: Lina
authors: L
authors: Peng
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|b Key Laboratory of Ministry of Education , Department of Molecular Biology, Fudan University , Shanghai , China.
authors: Liping
authors: L
authors: Zhao
authors: f School of Computer Science & State Key Laboratory of High Performance Computing, National University of Defense Technology , Changsha , China.
authors: Shaoliang
authors: S
authors: Peng
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|b Key Laboratory of Ministry of Education , Department of Molecular Biology, Fudan University , Shanghai , China.
authors: Yao
authors: Y
authors: Xiao
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|b Key Laboratory of Ministry of Education , Department of Molecular Biology, Fudan University , Shanghai , China.
authors: Shihua
authors: S
authors: Dong
authors: e The Experimental Training Center for Basic Medical Sciences, The Second Military Medical University , Shanghai , China.
authors: Jie
authors: J
authors: Cao
authors: a Laboratory of RNA Epigenetics , Institutes of Biomedical Sciences & Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University , Shanghai , China.|b Key Laboratory of Ministry of Education , Department of Molecular Biology, Fudan University , Shanghai , China.|c Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University , Shanghai , China.
authors: Wenqiang
authors: W
authors: Yu
mesh_terms: D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D030541:Databases, Genetic; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012319:RNA Polymerase II / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D006657:Histones; C543845:MIRN24 microRNA, human; D035683:MicroRNAs; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D012319:RNA Polymerase II
keywords: Chromatin modification; enhancer; miR-24; microRNA; nucleus; transcriptional activation