Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs

Circular RNAs (circRNAs) are evolutionarily conserved and abundant non-coding RNAs whose functions and regulatory mechanisms remain largely unknown. Here, we identify and characterize an epigenomically distinct group of circRNAs (TAH-circRNAs), which are transcribed to a higher level than their host...

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Published inFrontiers in genetics Vol. 11; p. 590672
Main Authors Li, Xue-Cang, Tang, Zhi-Dong, Peng, Li, Li, Yan-Yu, Qian, Feng-Cui, Zhao, Jian-Mei, Ding, Ling-Wen, Du, Xiao-Juan, Li, Meng, Zhang, Jian, Bai, Xue-Feng, Zhu, Jiang, Feng, Chen-Chen, Wang, Qiu-Yu, Pan, Jian, Li, Chun-Quan
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 25.01.2021
Subjects
circular RNAs
epigenomic
Genetics
TAH-circRNAs
transcription factors
transcriptional regulation
TAH-circRNAs
epigenomic
circular RNAs
transcription factors
transcriptional regulation
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Summary:Circular RNAs (circRNAs) are evolutionarily conserved and abundant non-coding RNAs whose functions and regulatory mechanisms remain largely unknown. Here, we identify and characterize an epigenomically distinct group of circRNAs (TAH-circRNAs), which are transcribed to a higher level than their host genes. By integrative analysis of cistromic and transcriptomic data, we find that compared with other circRNAs, TAH-circRNAs are expressed more abundantly and have more transcription factors (TFs) binding sites and lower DNA methylation levels. Concordantly, TAH-circRNAs are enriched in open and active chromatin regions. Importantly, ChIA-PET results showed that 23-52% of transcription start sites (TSSs) of TAH-circRNAs have direct interactions with cis-regulatory regions, strongly suggesting their independent transcriptional regulation from host genes. In addition, we characterize molecular features of super-enhancer-driven circRNAs in cancer biology. Together, this study comprehensively analyzes epigenomic characteristics of circRNAs and identifies a distinct group of TAH-circRNAs that are independently transcribed via enhancers and super-enhancers by TFs. These findings substantially advance our understanding of the regulatory mechanism of circRNAs and may have important implications for future investigations of this class of non-coding RNAs.
Bibliography:Reviewed by: Geetha Durairaj, University of California, Irvine, United States; Giuseppe Biamonti, National Research Council (CNR), Italy
Edited by: Graziano Pesole, University of Bari Aldo Moro, Italy
These authors have contributed equally to this work and share first authorship
This article was submitted to RNA, a section of the journal Frontiers in Genetics
ISSN:1664-8021
1664-8021
DOI:10.3389/fgene.2020.590672