Nascent RNA sequencing analysis provides insights into enhancer-mediated gene regulation
Abstract Background Enhancers are distal cis-regulatory elements that control gene expression. Despite an increasing appreciation of the importance of enhancers in cellular function and disease, our knowledge of enhancer-regulated transcription is very limited. Nascent RNA sequencing technologies, s...
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| Format: | Article |
| Language: | English |
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BMC
2018-08-01
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| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12864-018-5016-z |
| _version_ | 1811280332566036480 |
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| author | Jing Wang Yue Zhao Xiaofan Zhou Scott W. Hiebert Qi Liu Yu Shyr |
| author_facet | Jing Wang Yue Zhao Xiaofan Zhou Scott W. Hiebert Qi Liu Yu Shyr |
| author_sort | Jing Wang |
| collection | DOAJ |
| description | Abstract Background Enhancers are distal cis-regulatory elements that control gene expression. Despite an increasing appreciation of the importance of enhancers in cellular function and disease, our knowledge of enhancer-regulated transcription is very limited. Nascent RNA sequencing technologies, such as global nuclear run-on sequencing (GRO-seq) and precision run-on sequencing (PRO-seq), not only provide a direct and reliable measurement of enhancer activity, but also allow for quantifying transcription of enhancers and target genes simultaneously, making these technologies extremely useful for exploring enhancer-mediated regulation. Results Nascent RNA sequencing analysis (NRSA) provides a comprehensive view of enhancer-mediated gene regulation. NRSA not only outperforms existing methods for enhancer identification, but also enables annotation and quantification of active enhancers, and prediction of their target genes. Furthermore, NRSA identifies functionally important enhancers by integrating 1) nascent transcriptional changes in enhancers and their target genes and 2) binding profiles from regulator(s) of interest. Applied to wildtype and histone deacetylase 3 (Hdac3) knockout mouse livers, NRSA showed that HDAC3 regulates RNA polymerase recruitment through both proximal (promoter) and distal (enhancer) regulatory elements. Integrating ChIP-seq with PRO-seq data, NRSA prioritized enhancers based on their potential contribution to mediating HDAC3 regulation. Conclusions NRSA will greatly facilitate the usage of nascent RNA sequencing techniques and accelerate the study of enhancer-mediated regulation. |
| first_indexed | 2024-04-13T01:11:46Z |
| format | Article |
| id | doaj.art-05443fe2874e4f63a3689dcfaf2da9d6 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-13T01:11:46Z |
| publishDate | 2018-08-01 |
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| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-05443fe2874e4f63a3689dcfaf2da9d62022-12-22T03:09:07ZengBMCBMC Genomics1471-21642018-08-0119111810.1186/s12864-018-5016-zNascent RNA sequencing analysis provides insights into enhancer-mediated gene regulationJing Wang0Yue Zhao1Xiaofan Zhou2Scott W. Hiebert3Qi Liu4Yu Shyr5Center for Quantitative Sciences, Vanderbilt University Medical CenterDepartment of Biochemistry, Vanderbilt University School of MedicineDepartment of Biological Science, Vanderbilt UniversityDepartment of Biochemistry, Vanderbilt University School of MedicineCenter for Quantitative Sciences, Vanderbilt University Medical CenterCenter for Quantitative Sciences, Vanderbilt University Medical CenterAbstract Background Enhancers are distal cis-regulatory elements that control gene expression. Despite an increasing appreciation of the importance of enhancers in cellular function and disease, our knowledge of enhancer-regulated transcription is very limited. Nascent RNA sequencing technologies, such as global nuclear run-on sequencing (GRO-seq) and precision run-on sequencing (PRO-seq), not only provide a direct and reliable measurement of enhancer activity, but also allow for quantifying transcription of enhancers and target genes simultaneously, making these technologies extremely useful for exploring enhancer-mediated regulation. Results Nascent RNA sequencing analysis (NRSA) provides a comprehensive view of enhancer-mediated gene regulation. NRSA not only outperforms existing methods for enhancer identification, but also enables annotation and quantification of active enhancers, and prediction of their target genes. Furthermore, NRSA identifies functionally important enhancers by integrating 1) nascent transcriptional changes in enhancers and their target genes and 2) binding profiles from regulator(s) of interest. Applied to wildtype and histone deacetylase 3 (Hdac3) knockout mouse livers, NRSA showed that HDAC3 regulates RNA polymerase recruitment through both proximal (promoter) and distal (enhancer) regulatory elements. Integrating ChIP-seq with PRO-seq data, NRSA prioritized enhancers based on their potential contribution to mediating HDAC3 regulation. Conclusions NRSA will greatly facilitate the usage of nascent RNA sequencing techniques and accelerate the study of enhancer-mediated regulation.http://link.springer.com/article/10.1186/s12864-018-5016-zEnhancerNascent RNA sequencingEnhancer regulationEnhancer prioritization |
| spellingShingle | Jing Wang Yue Zhao Xiaofan Zhou Scott W. Hiebert Qi Liu Yu Shyr Nascent RNA sequencing analysis provides insights into enhancer-mediated gene regulation BMC Genomics Enhancer Nascent RNA sequencing Enhancer regulation Enhancer prioritization |
| title | Nascent RNA sequencing analysis provides insights into enhancer-mediated gene regulation |
| title_full | Nascent RNA sequencing analysis provides insights into enhancer-mediated gene regulation |
| title_fullStr | Nascent RNA sequencing analysis provides insights into enhancer-mediated gene regulation |
| title_full_unstemmed | Nascent RNA sequencing analysis provides insights into enhancer-mediated gene regulation |
| title_short | Nascent RNA sequencing analysis provides insights into enhancer-mediated gene regulation |
| title_sort | nascent rna sequencing analysis provides insights into enhancer mediated gene regulation |
| topic | Enhancer Nascent RNA sequencing Enhancer regulation Enhancer prioritization |
| url | http://link.springer.com/article/10.1186/s12864-018-5016-z |
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