Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs

Xue-Cang Li, Zhi-Dong Tang, Li Peng, Yan-Yu Li, Feng-Cui Qian, Jian-Mei Zhao, Ling-Wen Ding, Xiao-Juan Du, Meng Li, Jian Zhang, Xue-Feng Bai, Jiang Zhu (+4 others)
<span title="2021-01-25">2021</span> <i title="Frontiers Media SA"> <a target="_blank" rel="noopener" href="" style="color: black;">Frontiers in Genetics</a> </i> &nbsp;
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)
more &raquo; ... nding 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.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="">doi:10.3389/fgene.2020.590672</a> <a target="_blank" rel="external noopener" href="">pmid:33569079</a> <a target="_blank" rel="external noopener" href="">pmcid:PMC7868561</a> <a target="_blank" rel="external noopener" href="">fatcat:odqxpoobz5bdpccqneustpxnmm</a> </span>
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