RRC ID 52710
Author Charney RM, Forouzmand E, Cho JS, Cheung J, Paraiso KD, Yasuoka Y, Takahashi S, Taira M, Blitz IL, Xie X, Cho KW.
Title Foxh1 Occupies cis-Regulatory Modules Prior to Dynamic Transcription Factor Interactions Controlling the Mesendoderm Gene Program.
Journal Dev Cell
Abstract 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.
Volume 40(6)
Pages 595-607.e4
Published 2017-3-27
DOI 10.1016/j.devcel.2017.02.017
PII S1534-5807(17)30086-2
PMID 28325473
PMC PMC5434453
MeSH Animals Blastula / metabolism Cleavage Stage, Ovum / metabolism Co-Repressor Proteins / metabolism Embryo, Nonmammalian / metabolism Endoderm / embryology Endoderm / metabolism* Enhancer Elements, Genetic / genetics Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism* Gene Expression Regulation, Developmental* Genome Histones / metabolism Lysine / metabolism Mesoderm / embryology Mesoderm / metabolism* Methylation Nodal Protein / metabolism Protein Binding / genetics RNA Polymerase II / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Regulatory Sequences, Nucleic Acid / genetics Sequence Analysis, RNA Signal Transduction / genetics Transcription Factors / metabolism* Transcription, Genetic Xenopus / embryology* Xenopus / genetics* Xenopus / metabolism Xenopus Proteins / genetics Xenopus Proteins / metabolism*
IF 10.092
Times Cited 20
Clawed frogs / Newts Xenopus tropicalis