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Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs
<span title="2021-01-25">2021</span>
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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)
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<a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.3389/fgene.2020.590672">doi:10.3389/fgene.2020.590672</a>
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... 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.
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