Hybridization led to a rewired pluripotency network in Xenopus laevis [CUT&RUN]

After fertilization, maternally contributed factors to the egg initiate the transition to pluripotency, in large part by activating de novo transcription from the embryonic genome. Diverse mechanisms coordinate this transition across animals, suggesting that widespread evolutionary innovation has shaped the earliest stages of development. Here, we show that homologs of mammalian reprogramming factors OCT4 and SOX2 divergently regulate the two subgenomes of the allotetraploid Xenopus laevis, resulting in asymmetric activation of hundreds of homeologous gene pairs in the early embryo. Chromatin accessibility profiling and CUT&RUN for modified histones and transcription factor binding reveal extensive differences in enhancer architecture between the subgenomes, which likely arose after hybridization of X. laevis's diploid progenitors ~17 million years ago. However, comparison with diploid X. tropicalis shows broad conservation of embryonic gene expression levels when divergent homeolog contributions are combined, implying strong selection to maintain dosage in the pluripotency transcriptional program, amidst genomic instability following hybridization. Histone modification and transcription factor CUT&RUN was performed on Stage 8-10.5 embryos. Control samples were handled identically to CUT&RUN samples except without primary antibody addition.