Landscape of Enhancer-Enhancer Cooperative Regulation during Human Cardiac Commitment
Although accumulating evidence has demonstrated the key roles of enhancers in gene expression regulation, the contribution of genome-wide enhancer-enhancer interactions to developmental decisions remains unclear. Here we explored the cooperative regulation patterns among enhancers to understand thei...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-09-01
|
| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253119302057 |
| _version_ | 1828355120964829184 |
|---|---|
| author | Hong Chen Jun Xiao Tingting Shao Li Wang Jing Bai Xiaoyu Lin Na Ding Yinwei Qu Yi Tian Xiang Chen Hui Liu Hongyu Liu Juan Xu Xia Li |
| author_facet | Hong Chen Jun Xiao Tingting Shao Li Wang Jing Bai Xiaoyu Lin Na Ding Yinwei Qu Yi Tian Xiang Chen Hui Liu Hongyu Liu Juan Xu Xia Li |
| author_sort | Hong Chen |
| collection | DOAJ |
| description | Although accumulating evidence has demonstrated the key roles of enhancers in gene expression regulation, the contribution of genome-wide enhancer-enhancer interactions to developmental decisions remains unclear. Here we explored the cooperative regulation patterns among enhancers to understand their regulatory mechanism. We first filtered robust enhancers in embryonic stem cells (ESCs) through integrating bidirectional transcription, genomic location, and epigenetic modification. Genome-wide enhancer-enhancer interactions were then identified based on enhancer-promoter relationships that were derived from Hi-C data. We further explored the interacting principles of the identified enhancer-enhancer interactions. The results revealed that the observed cooperativity occurred mainly between enhancers distributed within a 1-kb to 10-Mb distance across the genome. In addition, enhancer-enhancer pairs had higher expression correlations than non-interacting pairs. Finally, we identified robust enhancers during human cardiac commitment, and we found that enhancers exhibited strong stage-specific expression patterns. We further inferred the enhancer-enhancer interactions based on RNA sequencing (RNA-seq) data in heart development, according to the regulatory principles characterized from Hi-C data. The identified enhancer-enhancer interaction networks (EEINs) presented highly dynamic linkages. Moreover, enhancers cooperatively targeted many marker genes in each developmental stage to regulate stage-specific functions, which contribute to the organization of cell identity in heart development. Our work will increase the understanding of enhancer regulation in human heart development. Keywords: enhancer, eRNA, histone modification, cooperative regulation, heart development, Hi-C, RNA-seq |
| first_indexed | 2024-04-14T02:37:11Z |
| format | Article |
| id | doaj.art-eddc539983564a4e8e4bc3b36b788833 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-14T02:37:11Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-eddc539983564a4e8e4bc3b36b7888332022-12-22T02:17:24ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-09-0117840851Landscape of Enhancer-Enhancer Cooperative Regulation during Human Cardiac CommitmentHong Chen0Jun Xiao1Tingting Shao2Li Wang3Jing Bai4Xiaoyu Lin5Na Ding6Yinwei Qu7Yi Tian8Xiang Chen9Hui Liu10Hongyu Liu11Juan Xu12Xia Li13College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China; Corresponding author: Hui Liu, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.Cardiovascular Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150081, China; Corresponding author: Hongyu Liu, Cardiovascular Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150081, China.College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China; Key Laboratory of Cardiovascular Medicine Research, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang 150081, China; Corresponding author: Juan Xu, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China; Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou 571199, China; Key Laboratory of Cardiovascular Medicine Research, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang 150081, China; Corresponding author: Xia Li, College of Bioinformatics Science and Technology, Harbin Medical University, Heilongjiang 150081, China.Although accumulating evidence has demonstrated the key roles of enhancers in gene expression regulation, the contribution of genome-wide enhancer-enhancer interactions to developmental decisions remains unclear. Here we explored the cooperative regulation patterns among enhancers to understand their regulatory mechanism. We first filtered robust enhancers in embryonic stem cells (ESCs) through integrating bidirectional transcription, genomic location, and epigenetic modification. Genome-wide enhancer-enhancer interactions were then identified based on enhancer-promoter relationships that were derived from Hi-C data. We further explored the interacting principles of the identified enhancer-enhancer interactions. The results revealed that the observed cooperativity occurred mainly between enhancers distributed within a 1-kb to 10-Mb distance across the genome. In addition, enhancer-enhancer pairs had higher expression correlations than non-interacting pairs. Finally, we identified robust enhancers during human cardiac commitment, and we found that enhancers exhibited strong stage-specific expression patterns. We further inferred the enhancer-enhancer interactions based on RNA sequencing (RNA-seq) data in heart development, according to the regulatory principles characterized from Hi-C data. The identified enhancer-enhancer interaction networks (EEINs) presented highly dynamic linkages. Moreover, enhancers cooperatively targeted many marker genes in each developmental stage to regulate stage-specific functions, which contribute to the organization of cell identity in heart development. Our work will increase the understanding of enhancer regulation in human heart development. Keywords: enhancer, eRNA, histone modification, cooperative regulation, heart development, Hi-C, RNA-seqhttp://www.sciencedirect.com/science/article/pii/S2162253119302057 |
| spellingShingle | Hong Chen Jun Xiao Tingting Shao Li Wang Jing Bai Xiaoyu Lin Na Ding Yinwei Qu Yi Tian Xiang Chen Hui Liu Hongyu Liu Juan Xu Xia Li Landscape of Enhancer-Enhancer Cooperative Regulation during Human Cardiac Commitment Molecular Therapy: Nucleic Acids |
| title | Landscape of Enhancer-Enhancer Cooperative Regulation during Human Cardiac Commitment |
| title_full | Landscape of Enhancer-Enhancer Cooperative Regulation during Human Cardiac Commitment |
| title_fullStr | Landscape of Enhancer-Enhancer Cooperative Regulation during Human Cardiac Commitment |
| title_full_unstemmed | Landscape of Enhancer-Enhancer Cooperative Regulation during Human Cardiac Commitment |
| title_short | Landscape of Enhancer-Enhancer Cooperative Regulation during Human Cardiac Commitment |
| title_sort | landscape of enhancer enhancer cooperative regulation during human cardiac commitment |
| url | http://www.sciencedirect.com/science/article/pii/S2162253119302057 |
| work_keys_str_mv | AT hongchen landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment AT junxiao landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment AT tingtingshao landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment AT liwang landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment AT jingbai landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment AT xiaoyulin landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment AT nading landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment AT yinweiqu landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment AT yitian landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment AT xiangchen landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment AT huiliu landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment AT hongyuliu landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment AT juanxu landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment AT xiali landscapeofenhancerenhancercooperativeregulationduringhumancardiaccommitment |