CANTAC-seq analysis reveals E2f1 and Otx1 as a coupled repressor-activator pair co-modulating zygotic genome activation in Xenopus tropicalis

Abstract Zygotic genome activation (ZGA) is tightly associated with the modulation of chromatin accessibility via maternal transcription factors. However, due to technical limitations, it remains elusive how the chromatin regulatory landscape is established during Xenopus tropicalis (X. tropicalis) ZGA and DNA binding transcription regulators involved in this process have therefore been underexplored. Here, by developing CANTAC-seq, we generated a first genome-wide map of accessible chromatin of early X. tropicalis embryos and found that the open chromatin landscape is progressively established at cis-regulatory elements during ZGA. Based on the motif analysis and perturbation experiments, we demonstrated E2f1, a well-known transcriptional activator, maintains a repressive chromatin environment independent of its negative effect on cell cycle progression before the MBT. Moreover, we identified another maternal factor Otx1 counteracts the inhibitory function of E2f1. The dynamic balance between the two factors determines the temporal regulation of a set of genes required for zygotic gene transcription and germ layer differentiation.