AUTHOR=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 TITLE=Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs JOURNAL=Frontiers in Genetics VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.590672 DOI=10.3389/fgene.2020.590672 ISSN=1664-8021 ABSTRACT=

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.