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

[ Vol. 18 , Issue. 5 ]

Author(s):

Yan Wang, Yinping Xie, Lili Li, Yuan He, Di Zheng, Pengcheng Yu, Ling Yu, Lixu Tang, Yibin Wang* and Zhihua Wang*   Pages 275 - 285 ( 11 )

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.

Keywords:

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

Affiliation:

Department of Cardiovascular Medicine, Beijing Hospital, National Center of Gerontology, Beijing 100730, Department of Cardiology, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060, Department of Cardiology, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060, Department of Cardiology, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060, Department of Orthopedics, Renmin Hospital, Wuhan University, Wuhan 430060, Department of Cardiology, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060, Department of Orthopedics, Renmin Hospital, Wuhan University, Wuhan 430060, Wushu College, Wuhan Sports University, Wuhan, Hubei 430079, Departments of Anesthesiology, Division of Molecular Medicine, Physiology and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, Department of Cardiology, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060



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