title: Genome-wide view of TGFβ/Foxh1 regulation of the early mesendoderm program.
abstract: Nodal/TGFβ signaling regulates diverse biological responses. By combining RNA-seq on Foxh1 and Nodal signaling loss-of-function embryos with ChIP-seq of Foxh1 and Smad2/3, we report a comprehensive genome-wide interaction between Foxh1 and Smad2/3 in mediating Nodal signaling during vertebrate mesendoderm development. This study significantly increases the total number of Nodal target genes regulated by Foxh1 and Smad2/3, and reinforces the notion that Foxh1-Smad2/3-mediated Nodal signaling directly coordinates the expression of a cohort of genes involved in the control of gene transcription, signaling pathway modulation and tissue morphogenesis during gastrulation. We also show that Foxh1 may function independently of Nodal signaling, in addition to its role as a transcription factor mediating Nodal signaling via Smad2/3. Finally, we propose an evolutionarily conserved interaction between Foxh1 and PouV, a mechanism observed in Pou5f1-mediated regulation of pluripotency in human embryonic stem and epiblast cells.
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, CA 92697-2300, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Chiu
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, CA 92697-2300, USA.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Charney Le
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, CA 92697-2300, USA.
authors.forename: Ira L
authors.initials: IL
authors.lastname: Blitz
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, CA 92697-2300, USA.
authors.forename: Margaret B
authors.initials: MB
authors.lastname: Fish
authors.affiliation: Department of Computer Science, University of California, Irvine, CA 92697-2300, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Computer Science, University of California, Irvine, CA 92697-2300, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Biesinger
authors.affiliation: Department of Computer Science, University of California, Irvine, CA 92697-2300, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, CA 92697-2300, USA kwcho@uci.edu.
authors.forename: Ken W Y
authors.initials: KW
authors.lastname: Cho
mesh_terms: D000818:Animals; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D004707:Endoderm / Q000196:embryology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D047468:Immunoprecipitation; D008648:Mesoderm / Q000196:embryology*; D060172:Morpholinos / Q000235:genetics; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C102067:FOXH1 protein, Xenopus; D051858:Forkhead Transcription Factors; D060172:Morpholinos; D055457:Nodal Protein; D051899:Smad2 Protein; C497785:Smad2 protein, Xenopus; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins
keywords: Cell fate; ChIP-seq; Foxh1; Genomics; Mesendoderm; Morphogenesis; Oct4; Pou5f1; RNA-seq; Signaling; Smad; TGFβ; Xenopus tropicalis