title: Divergent lncRNAs Regulate Gene Expression and Lineage Differentiation in Pluripotent Cells.
abstract: Divergent lncRNAs that are transcribed in the opposite direction to nearby protein-coding genes comprise a significant proportion (∼20%) of total lncRNAs in mammalian genomes. Through genome-wide analysis, we found that the distribution of this lncRNA class strongly correlates with essential developmental regulatory genes. In pluripotent cells, divergent lncRNAs regulate the transcription of nearby genes. As an example, the divergent lncRNA Evx1as promotes transcription of its neighbor gene, EVX1, and regulates mesendodermal differentiation. At a single-cell level, early broad expression of Evx1as is followed by a rapid, high-level transcription of EVX1, supporting the idea that Evx1as plays an upstream role to facilitate EVX1 transcription. Mechanistically, Evx1as RNA binds to regulatory sites on chromatin, promotes an active chromatin state, and interacts with Mediator. Based on our analyses, we propose that the biological function of thousands of uncharacterized lncRNAs of this class may be inferred from the role of their neighboring adjacent genes.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Sai
authors.initials: S
authors.lastname: Luo
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: J Yuyang
authors.initials: JY
authors.lastname: Lu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Liu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Bohou
authors.initials: B
authors.lastname: Wu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Ronggang
authors.initials: R
authors.lastname: Xu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Pixi
authors.initials: P
authors.lastname: Yan
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Shao
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Na
authors.affiliation: Biodynamic Optical Imaging Center, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Fuchou
authors.initials: F
authors.lastname: Tang
authors.affiliation: The Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yong E
authors.initials: YE
authors.lastname: Zhang
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: xshen@tsinghua.edu.cn.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Shen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D002843:Chromatin / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004707:Endoderm / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D056426:Genetic Loci; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056892:Mediator Complex / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D009690:Nucleic Acid Conformation; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D016372:RNA, Antisense / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D059010:Single-Cell Analysis; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; C489555:Evx1 protein, mouse; D018398:Homeodomain Proteins; D056892:Mediator Complex; D016372:RNA, Antisense; D062085:RNA, Long Noncoding
keywords: ESCs; Evx1as; development; divergent lncRNA; transcription regulation