EZH2 RIP-seq Identifies Tissue-specific Long Non-coding RNAs

Title:EZH2 RIP-seq Identifies Tissue-specific Long Non-coding RNAs

Volume: 18 Issue: 5

Author(s): Yan Wang, Yinping Xie, Lili Li, Yuan He, Di Zheng, Pengcheng Yu, Ling Yu, Lixu Tang, Yibin Wang*Zhihua Wang*

Affiliation:

• Departments of Anesthesiology, Division of Molecular Medicine, Physiology and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095,United States

• Department of Cardiology, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060,China

Keywords: Epigenetics, Long non-coding RNA, Tissue specificity, PRC2, EZH2, Histone methylation.

Abstract: Background: Polycomb Repressive Complex 2 (PRC2) catalyzes histone methylation at H3 Lys27, and plays crucial roles during development and diseases in numerous systems. Its catalytic subunit EZH2 represents a key nuclear target for long non-coding RNAs (lncRNAs) that emerging to be a novel class of epigenetic regulator and participate in diverse cellular processes. LncRNAs are characterized by high tissue-specificity; however, little is known about the tissue profile of the EZH2- interacting lncRNAs.

Objective: Here we performed a global screening for EZH2-binding lncRNAs in tissues including brain, lung, heart, liver, kidney, intestine, spleen, testis, muscle and blood by combining RNA immuno- precipitation and RNA sequencing. We identified 1328 EZH2-binding lncRNAs, among which 470 were shared in at least two tissues while 858 were only detected in single tissue. An RNA motif with specific secondary structure was identified in a number of lncRNAs, albeit not in all EZH2-binding lncRNAs. The EZH2-binding lncRNAs fell into four categories including intergenic lncRNA, antisense lncRNA, intron-related lncRNA and promoter-related lncRNA, suggesting diverse regulations of both cis and trans-mechanisms. A promoter-related lncRNA Hnf1aos1 bound to EZH2 specifically in the liver, a feature same as its paired coding gene Hnf1a, further confirming the validity of our study. In addition to the well known EZH2-binding lncRNAs like Kcnq1ot1, Gas5, Meg3, Hotair and Malat1, majority of the lncRNAs were firstly reported to be associated with EZH2.

Conclusion: Our findings provide a profiling view of the EZH2-interacting lncRNAs across different tissues, and suggest critical roles of lncRNAs during cell differentiation and maturation.

Cite this article as:

Wang Yan , Xie Yinping , Li Lili , He Yuan , Zheng Di , Yu Pengcheng , Yu Ling , Tang Lixu , Wang Yibin *, Wang Zhihua *, EZH2 RIP-seq Identifies Tissue-specific Long Non-coding RNAs, Current Gene Therapy 2018; 18 (5) . https://dx.doi.org/10.2174/1566523218666181008125010