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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2020.590672/full |
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| author | 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 Chen-Chen Feng Qiu-Yu Wang Jian Pan Chun-Quan Li |
| author_facet | 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 Chen-Chen Feng Qiu-Yu Wang Jian Pan Chun-Quan Li |
| author_sort | Xue-Cang Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T19:16:01Z |
| format | Article |
| id | doaj.art-ddcfa2caaa8848eba7110c7b01cbbeb9 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-17T19:16:01Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-ddcfa2caaa8848eba7110c7b01cbbeb92022-12-21T21:35:45ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-01-011110.3389/fgene.2020.590672590672Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAsXue-Cang Li0Zhi-Dong Tang1Li Peng2Yan-Yu Li3Feng-Cui Qian4Jian-Mei Zhao5Ling-Wen Ding6Xiao-Juan Du7Meng Li8Jian Zhang9Xue-Feng Bai10Jiang Zhu11Chen-Chen Feng12Qiu-Yu Wang13Jian Pan14Chun-Quan Li15School of Medical Informatics, Harbin Medical University, Daqing, ChinaSchool of Medical Informatics, Harbin Medical University, Daqing, ChinaGuangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaSchool of Medical Informatics, Harbin Medical University, Daqing, ChinaSchool of Medical Informatics, Harbin Medical University, Daqing, ChinaSchool of Medical Informatics, Harbin Medical University, Daqing, ChinaCancer Science Institute of Singapore, National University of Singapore, Singapore, SingaporeThe 942 Hospital of Joint Logistic Support Force of PLA, Yinchuan, ChinaSchool of Medical Informatics, Harbin Medical University, Daqing, ChinaSchool of Medical Informatics, Harbin Medical University, Daqing, ChinaSchool of Medical Informatics, Harbin Medical University, Daqing, ChinaSchool of Medical Informatics, Harbin Medical University, Daqing, ChinaSchool of Medical Informatics, Harbin Medical University, Daqing, ChinaSchool of Medical Informatics, Harbin Medical University, Daqing, ChinaDepartment of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, ChinaSchool of Medical Informatics, Harbin Medical University, Daqing, ChinaCircular 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.https://www.frontiersin.org/articles/10.3389/fgene.2020.590672/fulltranscription factorstranscriptional regulationepigenomiccircular RNAsTAH-circRNAs |
| spellingShingle | 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 Chen-Chen Feng Qiu-Yu Wang Jian Pan Chun-Quan Li Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs Frontiers in Genetics transcription factors transcriptional regulation epigenomic circular RNAs TAH-circRNAs |
| title | Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs |
| title_full | Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs |
| title_fullStr | Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs |
| title_full_unstemmed | Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs |
| title_short | Integrative Epigenomic Analysis of Transcriptional Regulation of Human CircRNAs |
| title_sort | integrative epigenomic analysis of transcriptional regulation of human circrnas |
| topic | transcription factors transcriptional regulation epigenomic circular RNAs TAH-circRNAs |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2020.590672/full |
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