TY - JOUR
T1 - CNEReg Interprets Ruminant-specific Conserved Non-coding Elements by Developmental Gene Regulatory Network
AU - Pan, Xiangyu
AU - Ma, Zhaoxia
AU - Sun, Xinqi
AU - Li, Hui
AU - Zhang, Tingting
AU - Zhao, Chen
AU - Wang, Nini
AU - Heller, Rasmus
AU - Hung Wong, Wing
AU - Wang, Wen
AU - Jiang, Yu
AU - Wang, Yong
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
KW - Conserved non-coding element
KW - Gene regulatory network
KW - Ruminant
KW - Toolkit transcription factor
KW - Trait innovation
UR - http://www.scopus.com/inward/record.url?scp=85176452581&partnerID=8YFLogxK
U2 - 10.1016/j.gpb.2022.11.007
DO - 10.1016/j.gpb.2022.11.007
M3 - 文章
C2 - 36494035
AN - SCOPUS:85176452581
SN - 1672-0229
VL - 21
SP - 632
EP - 648
JO - Genomics, Proteomics and Bioinformatics
JF - Genomics, Proteomics and Bioinformatics
IS - 3
ER -