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

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

Genomics, Proteomics & Bioinformatics (Jun 2023)

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

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

Affiliations

Xiangyu Pan: Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China; Department of Medical Research, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China; Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
Zhaoxia Ma: Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China; School of Mathematics, University of Chinese Academy of Sciences, Beijing 100049, China
Xinqi Sun: Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China; School of Mathematics, University of Chinese Academy of Sciences, Beijing 100049, China
Hui Li: Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530005, China
Tingting Zhang: Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China
Chen Zhao: Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China
Nini Wang: Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China
Rasmus Heller: Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen DK-2100, Denmark
Wing Hung Wong: Department of Statistics, Department of Biomedical Data Science, Bio-X Program, Stanford University, Stanford, CA 94305, USA
Wen Wang: Center for Ecological and Environmental Sciences, Northwestern Polytechnical University, Xi’an 710072, China; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China; Corresponding authors.
Yu Jiang: Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China; Corresponding authors.
Yong Wang: Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China; School of Mathematics, University of Chinese Academy of Sciences, Beijing 100049, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China; Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; Corresponding authors.

Journal volume & issue: Vol. 21, no. 3
pp. 632 – 648

Abstract

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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 ruminant-specific conserved non-coding elements (active-RSCNEs). To interpret the function of these active-RSCNEs, we defined toolkit transcription factors (TTFs) and modeled their regulation on rumen-specific 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.

Published in Genomics, Proteomics & Bioinformatics

ISSN: 1672-0229 (Print); 2210-3244 (Online)
Publisher: Oxford University Press
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General); Medicine: Medicine (General): Computer applications to medicine. Medical informatics
Website: https://academic.oup.com/gpb

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