Interpreting ruminant specific conserved non-coding elements by developmental gene regulatory network

Background Biologists long recognized that the genetic information encoded in DNA leads to trait innovation via gene regulatory network (GRN) in development. Results Here, we generated paired expression and chromatin accessibility data during rumen and esophagus development in sheep and revealed 1,601 active ruminant-specific conserved non-coding elements (active-RSCNEs). To interpret the function of these active-RSCNEs, we developed a Conserved Non-coding Element interpretation method by gene Regulatory network (CNEReg) to define toolkit transcription factors (TTF) and model its regulation on rumen specific gene via batteries of active-RSCNEs during development. Our developmental GRN reveals 18 TTFs and 313 active-RSCNEs regulating the functional modules of the rumen and identifies OTX1, SOX21, HOXC8, SOX2, TP63, PPARG and 16 active-RSCNEs that functionally distinguish the rumen from the esophagus. Conclusions We argue that CNEReg is an attractive systematic approach to integrate evo-devo concepts with omics data to understand how gene regulation evolves and shapes complex traits.