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CNEReg Interprets Ruminant-specific Conserved Non-coding Elements by Developmental Gene Regulatory Network

Genomics, Proteomics & Bioinformatics 2023年第3期21卷 632-648页

作者： Xiangyu Pan Zhaoxia Ma Xinqi Sun Hui Li Tingting Zhang Chen Zhao Nini Wang Rasmus Heller Wing Hung Wong Wen Wang Yu Jiang Yong Wang Key Laboratory of Animal Genetics Breeding and Reproduction of Shaanxi ProvinceCollege of Animal Science and TechnologyNorthwest A&F UniversityYangling 712100China Department of Medical Research Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Guangdong Cardiovascular Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Academy of Mathematics and Systems Science Chinese Academy of SciencesBeijing 100190China School of Mathematics University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources College of Animal Science and TechnologyGuangxi UniversityNanning 530005China Section for Computational and RNA Biology Department of BiologyUniversity of CopenhagenCopenhagen DK-2100Denmark Department of Statistics Department of Biomedical Data ScienceBio-X ProgramStanford UniversityStanfordCA 94305USA Center for Ecological and Environmental Sciences Northwestern Polytechnical UniversityXi’an 710072China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China

The genetic information coded in DNA leads to trait innovation via a gene regulatory network(GRN)in development.Here,we developed a conserved non-coding element interpretation method to integrate multi-omics data into gene regulatory network(CNEReg)to investigate the ruminant multi-chambered stomach innovation.We generated paired expression and chromatin accessibility data during rumen and esophagus development in sheep,and revealed 1601 active ruminantspecific conserved non-coding elements(active-RSCNEs).To interpret the function of these activeRSCNEs,we defined toolkit transcription factors(TTFs)and modeled their regulation on rumenspecific genes via batteries of active-RSCNEs during development.Our developmental GRN revealed 18 TTFs and 313 active-RSCNEs regulating 7 rumen functional modules.Notably,6 TTFs(OTX1,SOX21,HOXC8,SOX2,TP63,and PPARG),as well as 16 active-RSCNEs,functionally distinguished the rumen from the esophagus.Our study provides a systematic approach to understanding how gene regulation evolves and shapes complex traits by putting evo-devo concepts into practice with developmental multi-omics data.

关键词： Trait innovation Gene regulatory network Conserved non-coding element toolkit transcription factor Ruminant

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