Endodermal Maternal Transcription Factors Establish Super-Enhancers during Zygotic Genome Activation

Abstract

Summary: Elucidation of the sequence of events underlying the dynamic interaction between transcription factors and chromatin states is essential. Maternal transcription factors function at the top of the regulatory hierarchy to specify the primary germ layers at the onset of zygotic genome activation (ZGA). We focus on the formation of endoderm progenitor cells and examine the interactions between maternal transcription factors and chromatin state changes underlying the cell specification process. Endoderm-specific factors Otx1 and Vegt together with Foxh1 orchestrate endoderm formation by coordinated binding to select regulatory regions. These interactions occur before the deposition of enhancer histone marks around the regulatory regions, and these TFs recruit RNA polymerase II, regulate enhancer activity, and establish super-enhancers associated with important endodermal genes. Therefore, maternal transcription factors Otx1, Vegt, and Foxh1 combinatorially regulate the activity of super-enhancers, which in turn activate key lineage-specifying genes during ZGA. : How do maternal transcription factors interact with chromatin regions to coordinate the endodermal gene regulatory program? Paraiso et al. demonstrate that combinatorial binding of maternal Otx1, Vegt, and Foxh1 to select enhancers and super-enhancers in the genome controls endodermal cell fate specification during zygotic gene activation. Keywords: Xenopus tropicalis, endoderm, germ layer specification, zygotic genome activation, super-enhancers, enhancer RNAs, histone marks, Otx1, Vegt, Foxh1