4.6 Article

Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs

Journal

FRONTIERS IN GENETICS
Volume 11, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2020.590672

Keywords

transcription factors; transcriptional regulation; epigenomic; circular RNAs; TAH-circRNAs

Funding

  1. National Natural Science Foundation of China [61601150, 81572341, 81972658]
  2. Natural Science Foundation for Distinguished Young Scholars of Heilongjiang Province of China [JQ2020C004]
  3. YuWeihan Outstanding Youth Training Fund of Harbin Medical University (Daqing) [DQWLD201703]
  4. Natural Science Foundation of Heilongjiang Province [YQ2019C013]
  5. Post-doctoral Researchers in Heilongjiang Scientific Research Grants
  6. Yu Weihan Outstanding Youth Training Fund of Harbin Medical University

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This study identified a distinct group of circRNAs (TAH-circRNAs) with epigenomically unique features, independently transcribed via enhancers and super-enhancers by TFs and playing roles in cancer biology.
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.

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