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

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  • Xiangyu Pan
  • Zhaoxia Ma
  • Xinqi Sun
  • Hui Li
  • Tingting Zhang
  • Chen Zhao
  • Nini Wang
  • Heller, Rasmus
  • Wing Hung Wong
  • Wen Wang
  • Yu Jiang
  • Yong Wang
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.
OriginalsprogEngelsk
TidsskriftGenomics, Proteomics and Bioinformatics
Vol/bind21
Udgave nummer3
Sider (fra-til)632-648
Antal sider17
ISSN1672-0229
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This work was supported by the National Key R&D Program of China (Grant No. 2020YFA0712402), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDPB17), the CAS Project for Young Scientists in Basic Research (Grant No. YSBR-077), the National Natural Science Foundation of China (Grants Nos. 12025107, 11871463, 11688101, and 61621003), the National Thousand Youth Talents Plan, and the CAS “Light of West China” Program (Grant No. xbzg-zdsys-201913), China. We thank High-Performance Computing (HPC) of Northwest A&F University (NWAFU) for providing computing resources.

Funding Information:
This work was supported by the National Key R&D Program of China (Grant No. 2020YFA0712402 ), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDPB17 ), the CAS Project for Young Scientists in Basic Research (Grant No. YSBR-077 ), the National Natural Science Foundation of China (Grants Nos. 12025107 , 11871463 , 11688101 , and 61621003 ), the National Thousand Youth Talents Plan, and the CAS “Light of West China” Program (Grant No. xbzg-zdsys-201913 ), China. We thank High-Performance Computing (HPC) of Northwest A&F University (NWAFU) for providing computing resources.

Publisher Copyright:
© 2022 The Authors

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