A SINGLE CELL CHROMATIN ACCESSIBILITY ATLAS OF THE DEVELOPING BOVINE PLACENTA

Thelong-term goalsof this project are to lay a foundation for understanding how chromatin dynamics and genome regulation influences cattle fertility and enable producers to select animals more effectively for increased reproductive efficiency. This proposal will facilitate the completion of a research project with thegoal of enhancing sustainability and security of food sources produced by cattle by ensuring efficient reproduction.The central hypothesisof this project isthat gene regulatory elements are critical drivers of placental development and associated reproductive traits in cattle. Specific goals of this project are to define regulatory elements in cell populations of the bovine placenta during development, and overlay genetic variation associated with reproductive traits to determine if they reside in regulatory regions. Two specific objectives are proposed to interrogate the central hypothesis: Objective 1: Define open chromatin regions, transcription factor binding sites, and predicted cis-regulatory elements across cell populations of the bovine placenta during early gestation (day 40 when cotyledons arise) and mid-gestation (day 170, when placentomes are fully developed and functional) by implementing single nuclei Assay for Transposase-Accessible Chromatin with sequencing (ATAC-seq) paired with existing single nuclei RNA-seq. Objective 2: Examine enrichment of quantitative trait loci (QTL) in regulatory regions defined in this study in cell populations across development of the bovine placenta and computationally predict the biological consequences of these variants in specific cell types.