RT Journal Article
SR Electronic
T1 Global regulatory transitions at core promoters demarcate the mammalian germline cycle
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.30.361865
DO 10.1101/2020.10.30.361865
A1 Cvetesic, Nevena
A1 Borkowska, Malgorzata
A1 Hatanaka, Yuki
A1 Leitch, Harry G.
A1 Müller, Ferenc
A1 Yu, Changwei
A1 Vincent, Stéphane D.
A1 Tora, László
A1 Hajkova, Petra
A1 Lenhard, Boris
YR 2020
UL http://biorxiv.org/content/early/2020/10/30/2020.10.30.361865.abstract
AB Core promoters integrate regulatory inputs of genes1–3. Global dynamics of promoter usage can reveal systemic changes in how genomic sequence is interpreted by the cell. We previously discovered that early development in fish is associated with a genome-wide shift in how promoters are read: the switch from the oocyte-specific to the somatic-specific promoter usage observed during Zygotic Genome Activation (ZGA) represents one of the most dramatic instances of transcriptional regulatory rewiring known in the animal life cycle4 However, the key question of how and when the oocyte-specific pattern is established in the germ line has been hitherto impossible to answer, as well as whether this switch is universal across vertebrate development. Here we report the first analysis of promoter dynamics and code switching in the mammalian germ line. Using the Super Low Input Carrier-CAGE5, 6 (SLIC-CAGE) we show that mouse germline development starts with the somatic promoter code with a prominent switch to the maternal code occurring during follicular oogenesis. The sequence features underlying the shift from somatic to maternal code are conserved across vertebrates, despite large differences in promoter nucleotide compositions. Surprisingly, we also find that the promoters of gonadal germ cells diverge from the canonical somatic transcription initiation. This divergence is distinct from the promoter code used later by developing oocytes and reveals genome-wide promoter remodelling driven by alternative nucleosome positioning during early female and male germline development. Collectively, our findings establish promoter-level regulatory transitions as a central, conserved feature of the vertebrate life cycle.Competing Interest StatementThe authors have declared no competing interest.