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

1. Cell Rep. 2019 Jun 4;27(10):2962-2977.e5. doi: 10.1016/j.celrep.2019.05.013. Endodermal Maternal Transcription Factors Establish Super-Enhancers during Zygotic Genome Activation. Paraiso KD(1), Blitz IL(2), Coley M(2), Cheung J(2), Sudou N(3), Taira M(4), Cho KWY(5). Author information: (1)Department of Developmental and Cell Biology, University of California, Irvine, CA, USA; Center for Complex Biological Systems, University of California, Irvine, CA, USA. (2)Department of Developmental and Cell Biology, University of California, Irvine, CA, USA. (3)Department of Anatomy, Tokyo Women's Medical University, Tokyo, Japan. (4)Department of Biological Sciences, Chuo University, Tokyo, Japan. (5)Department of Developmental and Cell Biology, University of California, Irvine, CA, USA; Center for Complex Biological Systems, University of California, Irvine, CA, USA. Electronic address: kwcho@uci.edu. 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. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.celrep.2019.05.013 PMCID: PMC6610736 PMID: 31167141 [Indexed for MEDLINE] Conflict of interest statement: DECLARATION OF INTERESTS The authors declare no competing interests.