**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** EPIGENETIC MODIFICATIONS INCLUDE CHEMICAL CHANGES TO DNA AND RNA BASE PAIRS THAT CAN INFLUENCE GENE FUNCTION AND SUBSEQUENTLY AFFECT ECONOMICALLY IMPORTANT TRAITS IN LIVESTOCK SPECIES. THE COLLECTION OF SEQUENCES REPRESENTATIVE OF THE DNA IN A POPULATION OR PANGENOME, IS IMPORTANT TO CAPTURE THE BREADTH OF GENOMIC VARIATION BETWEEN BREEDS AND POPULATIONS OF LIVESTOCK SPECIES. HOWEVER, TO FULLY COMPREHEND DIVERSITY IN LIVESTOCK SPECIES, ONE MUST ALSO EXHAUSTIVELY CHARACTERIZE A VARIETY OF EPIGENETIC MODIFICATIONS SO THAT WE CAN TRULY UNDERSTAND VARIATION AT A MOLECULAR LEVEL. THE PROPOSED PROJECT IS DESIGNED TO ESTABLISH A CATTLE AND SHEEP PAN-EPIGENOME. TO ACCOMPLISH THIS GOAL, WE WILL COMPREHENSIVELY CHARACTERIZE EPIGENOMIC CONSERVATION AND DIVERSITY THROUGH EXAMINATION OF THE AMOUNT AND LOCATION OF METHYLATION ON DNA AND RNA, HISTONE MODIFICATIONS, OPEN CHROMATIN, CHROMATIN ACCESSIBILITY IN THE LIVER, MUSCLE, AND PREFRONTAL CORTEX OF MULTIPLE BREEDS OF CATTLE AND SHEEP. FINALLY, COMPARATIVE EPIGENOMICS WILL BE USED TO IDENTIFY ORTHOLOGOUS REGIONS OF THE SHEEP AND BOVINE EPIGENOMES THAT HARBOR CONSERVED EPIGENETIC MODIFICATIONS AND VARIANTS. CATALOGING EPIGENETIC DIVERSITY ACROSS CATTLE AND SHEEP WILL INCREASE OUR UNDERSTANDING OF HOW DIFFERENT GENOMES, EPIGENOMES, AND GENE PRODUCTS FROM DIVERSE BREEDS OF CATTLE AND SHEEP AFFECT A VARIETY OF IMPORTANT BIOLOGICAL PHENOTYPES, SUPPORTING MORE ACCURATE PREDICTION OF TRAITS AND IMPROVING BREEDING STRATEGIES.