Details

Autor(en) / Beteiligte

• Luo, Sai
• Lu, J. Yuyang
• Liu, Lichao
• Yin, Yafei
• Chen, Chunyan
• Han, Xue
• Wu, Bohou
• Xu, Ronggang
• Liu, Wei
• Yan, Pixi
• Shao, Wen
• Lu, Zhi
• Li, Haitao
• Na, Jie
• Tang, Fuchou
• Wang, Jianlong
• Zhang, Yong E.
• Shen, Xiaohua

Titel

Divergent lncRNAs Regulate Gene Expression and Lineage Differentiation in Pluripotent Cells

Ist Teil von

• Cell stem cell, 2016-05, Vol.18 (5), p.637-652

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Genomic organization of divergent lncRNAs correlates strongly with regulatory genes•Divergent lncRNAs regulate the expression of adjacent genes in pluripotent cells•The lncRNA Evx1as binds locally to chromatin and promotes EVX1 transcription in cis•Evx1as acts upstream of EVX1 to mediate mesendodermal lineage differentiation Based on broad genomic analysis and specific functional characterization in pluripotent cells, Luo and colleagues suggest that a major class of lncRNAs that is arranged divergently to nearby genes plays a role in transcriptional regulation to fine-tune gene expression and lineage differentiation.