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Genome-wide view of TGFβ/Foxh1 regulation of the early mesendoderm program.

Authors
  • Chiu, William T
  • Charney Le, Rebekah
  • Blitz, Ira L
  • Fish, Margaret B
  • Li, Yi
  • Biesinger, Jacob
  • Xie, Xiaohui
  • Cho, Ken W Y
Type
Published Article
Journal
Development
Publisher
The Company of Biologists
Publication Date
Dec 01, 2014
Volume
141
Issue
23
Pages
4537–4547
Identifiers
DOI: 10.1242/dev.107227
PMID: 25359723
Source
Medline
Keywords
License
Unknown

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.

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