CNEReg Interprets Ruminant-specific Conserved Non-coding Elements by Developmental Gene Regulatory Network
Abstract
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.
Publication Title
Genomics Proteomics and Bioinformatics
Recommended Citation
Pan, X., Ma, Z., Sun, X., Li, H., Zhang, T., Zhao, C., Wang, N., Heller, R., Hung Wong, W., Wang, W., Jiang, Y., & Wang, Y. (2023). CNEReg Interprets Ruminant-specific Conserved Non-coding Elements by Developmental Gene Regulatory Network. Genomics Proteomics and Bioinformatics, 21 (3), 632-648. https://doi.org/10.1016/j.gpb.2022.11.007
