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

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

Journal Name: Current Gene Therapy

Volume 18 , Issue 5 , 2018

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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.

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Article Details

VOLUME: 18
ISSUE: 5
Year: 2018
Page: [275 - 285]
Pages: 11
DOI: 10.2174/1566523218666181008125010

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