SRA

The pioneer transcription factor Zelda (ZLD) increases the accessibility of chromatin to promote the essential process of zygotic genome activation (ZGA) in the Drosophila early embryo. However, many genomic loci remain accessible in the absence of ZLD and are enriched for GA-rich DNA binding motifs. Therefore, we hypothesized that other pioneer TFs that function with ZLD have not yet been identified, especially those that bind to GA-rich motifs. CLAMP (Chromatin-linked adaptor for Male-specific lethal MSL proteins) is a GA-rich motif binding TF that is essential for early embryonic development. Here, we identify for the first time that CLAMP is a pioneer TF which interacts directly with nucleosomes, regulates zygotic genome activation, promotes chromatin accessibility, and facilitates the binding of ZLD to promoters. When ZLD is bound at a locus but does not regulate chromatin accessibility, CLAMP can often function redundantly to open the chromatin. Because ZGA is an essential process across metazoans, it is key to evolve redundant pioneer TFs to protect organisms from lethality that would be caused by loss of a single non-redundant factor. Overall design: ChIP-seq was used to measure CLAMP and ZLD occupancy to genome after clamp-i or zld-I in 0-2hr and 2-4hr embryos.