CANTAC-seq analysis reveals the maternal factors E2f1 and Otx1 co-modulate minor zygotic gene transcription by a seesaw model (CANTAC-seq)

The transition from maternal to zygotic gene expression during zygotic genome activation (ZGA) is tightly associated with chromatin accessibility modulated by maternal transcription factors. However, due to technical limitations, it remains elusive how the chromatin regulatory landscape is established in Xenopus tropicalis ZGA, and let alone DNA binding transcription regulators involved in this process. Here, by developing concanavalin A beads-based nucleus capture followed by Tn5-mediated accessible chromatin assay with sequencing (CANTAC-seq), we generated a first genome-wide map of accessible chromatin in X. tropicalis embryos from early blastula to neurula stage. We found that open chromatin landscape is progressively established at cis-regulatory elements during ZGA. Based on the motif analysis and perturbation experiments, we demostrated E2f1, a well-known transcriptional activator, maintains a repressive chromatin environment preceding minor ZGA. Moreover, we identified another maternal factor Otx1 counteracts the inhibitory function of E2f1. Mechanistically, E2f1 and Otx1 co-regulate a set of genes required for zygotic gene transcription and germ layer differentiation before the midblastula transition (MBT) through a seesaw model. Taken together, our data reveals the dynamic chromatin regulatory landscape that accompanies early development and elaborates on the function of a coupled transcriptional repressor-activator regulating zygotic gene transcription in a classical model organism.