Foxh1 Occupies cis-Regulatory Modules Prior to Dynamic Transcription Factor Interactions Controlling the Mesendoderm Gene Program

Publication date: Available online 17 March 2017
Source:Developmental Cell
Author(s): Rebekah M. Charney, Elmira Forouzmand, Jin Sun Cho, Jessica Cheung, Kitt D. Paraiso, Yuuri Yasuoka, Shuji Takahashi, Masanori Taira, Ira L. Blitz, Xiaohui Xie, Ken W.Y. Cho
The interplay between transcription factors and chromatin dictates gene regulatory network activity. Germ layer specification is tightly coupled with zygotic gene activation and, in most metazoans, is dependent upon maternal factors. We explore the dynamic genome-wide interactions of Foxh1, a maternal transcription factor that mediates Nodal/TGF-β signaling, with cis-regulatory modules (CRMs) during mesendodermal specification. Foxh1 marks CRMs during cleavage stages and recruits the co-repressor Tle/Groucho in the early blastula. We highlight a population of CRMs that are continuously occupied by Foxh1 and show that they are marked by H3K4me1, Ep300, and Fox/Sox/Smad motifs, suggesting interplay between these factors in gene regulation. We also propose a molecular "hand-off" between maternal Foxh1 and zygotic Foxa at these CRMs to maintain enhancer activation. Our findings suggest that Foxh1 functions at the top of a hierarchy of interactions by marking developmental genes for activation, beginning with the onset of zygotic gene expression.

Graphical abstract

Teaser

How maternal transcription factors control the onset of gene regulatory networks in the early embryo is poorly understood. Charney et al. demonstrate dynamic binding of maternal Foxh1 to the embryonic genome well before zygotic gene activation. They elucidate the temporal recruitment of co-factors to cis-regulatory modules controlling mesendoderm specification.


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