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

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)....

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Bibliographic Details
Published in:Cell reports (Cambridge) Vol. 27; no. 10; pp. 2962 - 2977.e5
Main Authors: Paraiso, Kitt D, Blitz, Ira L, Coley, Masani, Cheung, Jessica, Sudou, Norihiro, Taira, Masanori, Cho, Ken W Y
Format: Journal Article
Language:English
Published: United States Elsevier 04-06-2019
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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.
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AUTHOR CONTRIBUTIONS
K.D.P., K.W.Y.C., and I.L.B. designed the reported experiments and wrote the manuscript. K.D.P., K.W.Y.C., M.C., J.C., and I.L.B. performed the wet bench experiments. K.D.P. performed the bioinformatics analyses. N.S. and M.T. generated the Vegt antibody.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2019.05.013