PT - JOURNAL ARTICLE AU - Jingyue Ellie Duan AU - Leila E. Rieder AU - Annie Huang AU - William T. Jordan III AU - Mary McKenney AU - Scott Watters AU - Nicolas L. Fawzi AU - Erica N. Larschan TI - CLAMP and Zelda function together as pioneer transcription factors to promote <em>Drosophila</em> zygotic genome activation AID - 10.1101/2020.07.15.205054 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.07.15.205054 4099 - http://biorxiv.org/content/early/2020/07/15/2020.07.15.205054.short 4100 - http://biorxiv.org/content/early/2020/07/15/2020.07.15.205054.full AB - Because zygotic genome activation (ZGA) is an essential process across metazoans, it is key to evolve multiple pioneer transcription factors (TFs) to protect organisms from loss of a single factor. Pioneer TF Zelda (ZLD) is the only known factor which increases accessibility of chromatin to promote ZGA in the early Drosophila embryo. However, many genomic loci remain accessible without ZLD and have GA-rich motifs. Therefore, we hypothesized that other pioneer TFs that function with ZLD have not yet been identified in early embryos, especially those that bind to GA-rich motifs, such as CLAMP (Chromatin-linked adaptor for Male-specific lethal MSL proteins). Here, we determine that CLAMP is a novel pioneer TF which interacts directly with nucleosomes, regulates zygotic genome transcription, promotes chromatin accessibility, and facilitates the binding of ZLD to promoters. Thus, the maternal factor CLAMP functions with ZLD as a pioneer TF to open chromatin and drive zygotic genome activation.Competing Interest StatementThe authors have declared no competing interest.