Deciphering germline-specific transcription initiation codes (360G-Wellcome-217309_Z_19_Z)

Epigenetic reprogramming and transcription have been thoroughly studied in primordial germ cells (PGC). However, an unexplored aspect is the role of core-promoters in regulation and execution of this program. It was recently discovered that thousands of promoters undergo a change in basic rules for transcription start site (TSS) selection between maternal/oocyte and zygotic/somatic transcription, effectively switching from one overlapping promoter architecture to another upon zygotic genome activation. This also implies that there should be a switch in the opposite direction during germline development, but when and how this happens is unknown, along with how it affects genome regulation and organization. Here, we set to investigate TSS usage during mouse PGC differentiation and oogenesis using our low-input methodology for mapping TSSs. Specifically, we aim to: 1) capture the developmental stage and epigenetic context in which the TSS-switching occurs; 2) uncover the underlying regulatory mechanisms. Since we believe that comparative studies are powerful for revealing general rules of animal development, opposed to lineage-specific innovations, we shall take advantage of collaborations to expand the study to zebrafish and Drosophila. Long-term, we expect that our results will provide better understanding of PGCs and gametes and lead to more efficient in vitro specification protocols.