Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development

Boni A. Afouda; Yukio Nakamura; Sophie Shaw; Rebekah M Charney; Kitt D. Paraiso; Ira L. Blitz; Ken W.Y.  Cho; Stefan Hoppler

doi:10.1016/j.isci.2020.101314

Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development

Boni A. Afouda, Yukio Nakamura, Sophie Shaw, Rebekah M Charney, Kitt D. Paraiso, Ira L. Blitz, Ken W.Y. Cho, Stefan Hoppler^* (Corresponding Author)

^*Corresponding author for this work

University of California at Irvine

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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Abstract

While Wnt/β-catenin signaling is generally conserved and well understood, the regulatory mechanisms controlling context-specific direct Wnt target gene
expression in development and disease are still unclear. The onset of zygotic gene transcription in early embryogenesis represents an ideal, accessible experimental system to investigate context-specific direct Wnt target gene
regulation. We combine transcriptomics using RNA-seq with genome-wide β--catenin association using ChIP-seq to identify stage-specific direct Wnt
target genes. We propose coherent feed forward regulation involving two distinct classes of direct maternal Wnt target genes, which differ both in expression and persistence of β-catenin association. We discover that genomic β-catenin-association overlaps with Foxh1-associated regulatory sequences, and demonstrate that direct maternal Wnt target gene expression requires Foxh1 function and Nodal/Tgfβ signaling. Our results support a new paradigm for direct Wnt target gene co-regulation with context-specific mechanisms that will inform future studies of embryonic development and more widely stem cell-mediated homeostasis and human disease.

Original language	English
Article number	101314
Number of pages	34
Journal	iScience
Volume	23
Issue number	7
Early online date	25 Jun 2020
DOIs	https://doi.org/10.1016/j.isci.2020.101314
Publication status	Published - 24 Jul 2020

Bibliographical note

We thank Jessica Cheung (UC Irvine) and Yvonne Turnbull (University of
Aberdeen) for technical and management support; Gert Jan Veenstra (Radboud University, Nijmegen) for discussion; and Adam Lynch and Victor Velecela (University of Aberdeen), for comments on the manuscript. We also thank Professor Masanori Taira (University of Tokyo, currently Chuo University) and Dr Norihiro Sudou (Nara Institute of Science and Technology, currently Tokyo Women's Medical University) for the siamois antibody; and Professor Dan Kessler (University of Pennsylvania) for siamois constructs. This research was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) in the United Kingdom (BB/M001695/1) and by NIH in the United States (NIH GM126395). SH additionally acknowledges personal funding support as a Royal Society/Leverhulme Trust Senior Research Fellow (SRF\R1\191017).

Keywords

Ctnnb1
β-catenin
Wnt signaling
Zygotic Gene Activation
Mid-Blastula Transition
Axis induction
Biological Sciences
Molecular Biology
Developmental Biology
TRANSCRIPTION FACTORS
SIGNALING PATHWAYS
INDUCTION
BETA-CATENIN
MESODERM
DNA
SIAMOIS
WNT
EXPRESSION
BINDING

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Afouda_etal_iScience_Foxh1Noidal_VOR
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Cite this

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title = "Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development",

abstract = "While Wnt/β-catenin signaling is generally conserved and well understood, the regulatory mechanisms controlling context-specific direct Wnt target geneexpression in development and disease are still unclear. The onset of zygotic gene transcription in early embryogenesis represents an ideal, accessible experimental system to investigate context-specific direct Wnt target generegulation. We combine transcriptomics using RNA-seq with genome-wide β--catenin association using ChIP-seq to identify stage-specific direct Wnttarget genes. We propose coherent feed forward regulation involving two distinct classes of direct maternal Wnt target genes, which differ both in expression and persistence of β-catenin association. We discover that genomic β-catenin-association overlaps with Foxh1-associated regulatory sequences, and demonstrate that direct maternal Wnt target gene expression requires Foxh1 function and Nodal/Tgfβ signaling. Our results support a new paradigm for direct Wnt target gene co-regulation with context-specific mechanisms that will inform future studies of embryonic development and more widely stem cell-mediated homeostasis and human disease. ",

keywords = "Ctnnb1, β-catenin, Wnt signaling, Zygotic Gene Activation, Mid-Blastula Transition, Axis induction, Biological Sciences, Molecular Biology, Developmental Biology, TRANSCRIPTION FACTORS, SIGNALING PATHWAYS, INDUCTION, BETA-CATENIN, MESODERM, DNA, SIAMOIS, WNT, EXPRESSION, BINDING",

author = "Afouda, {Boni A.} and Yukio Nakamura and Sophie Shaw and Charney, {Rebekah M} and Paraiso, {Kitt D.} and Blitz, {Ira L.} and Cho, {Ken W.Y.} and Stefan Hoppler",

note = "We thank Jessica Cheung (UC Irvine) and Yvonne Turnbull (University of Aberdeen) for technical and management support; Gert Jan Veenstra (Radboud University, Nijmegen) for discussion; and Adam Lynch and Victor Velecela (University of Aberdeen), for comments on the manuscript. We also thank Professor Masanori Taira (University of Tokyo, currently Chuo University) and Dr Norihiro Sudou (Nara Institute of Science and Technology, currently Tokyo Women's Medical University) for the siamois antibody; and Professor Dan Kessler (University of Pennsylvania) for siamois constructs. This research was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) in the United Kingdom (BB/M001695/1) and by NIH in the United States (NIH GM126395). SH additionally acknowledges personal funding support as a Royal Society/Leverhulme Trust Senior Research Fellow (SRF\R1\191017).",

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doi = "10.1016/j.isci.2020.101314",

language = "English",

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AU - Afouda, Boni A.

AU - Nakamura, Yukio

AU - Shaw, Sophie

AU - Charney, Rebekah M

AU - Paraiso, Kitt D.

AU - Blitz, Ira L.

AU - Cho, Ken W.Y.

AU - Hoppler, Stefan

N1 - We thank Jessica Cheung (UC Irvine) and Yvonne Turnbull (University of Aberdeen) for technical and management support; Gert Jan Veenstra (Radboud University, Nijmegen) for discussion; and Adam Lynch and Victor Velecela (University of Aberdeen), for comments on the manuscript. We also thank Professor Masanori Taira (University of Tokyo, currently Chuo University) and Dr Norihiro Sudou (Nara Institute of Science and Technology, currently Tokyo Women's Medical University) for the siamois antibody; and Professor Dan Kessler (University of Pennsylvania) for siamois constructs. This research was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) in the United Kingdom (BB/M001695/1) and by NIH in the United States (NIH GM126395). SH additionally acknowledges personal funding support as a Royal Society/Leverhulme Trust Senior Research Fellow (SRF\R1\191017).

PY - 2020/7/24

Y1 - 2020/7/24

N2 - While Wnt/β-catenin signaling is generally conserved and well understood, the regulatory mechanisms controlling context-specific direct Wnt target geneexpression in development and disease are still unclear. The onset of zygotic gene transcription in early embryogenesis represents an ideal, accessible experimental system to investigate context-specific direct Wnt target generegulation. We combine transcriptomics using RNA-seq with genome-wide β--catenin association using ChIP-seq to identify stage-specific direct Wnttarget genes. We propose coherent feed forward regulation involving two distinct classes of direct maternal Wnt target genes, which differ both in expression and persistence of β-catenin association. We discover that genomic β-catenin-association overlaps with Foxh1-associated regulatory sequences, and demonstrate that direct maternal Wnt target gene expression requires Foxh1 function and Nodal/Tgfβ signaling. Our results support a new paradigm for direct Wnt target gene co-regulation with context-specific mechanisms that will inform future studies of embryonic development and more widely stem cell-mediated homeostasis and human disease.

AB - While Wnt/β-catenin signaling is generally conserved and well understood, the regulatory mechanisms controlling context-specific direct Wnt target geneexpression in development and disease are still unclear. The onset of zygotic gene transcription in early embryogenesis represents an ideal, accessible experimental system to investigate context-specific direct Wnt target generegulation. We combine transcriptomics using RNA-seq with genome-wide β--catenin association using ChIP-seq to identify stage-specific direct Wnttarget genes. We propose coherent feed forward regulation involving two distinct classes of direct maternal Wnt target genes, which differ both in expression and persistence of β-catenin association. We discover that genomic β-catenin-association overlaps with Foxh1-associated regulatory sequences, and demonstrate that direct maternal Wnt target gene expression requires Foxh1 function and Nodal/Tgfβ signaling. Our results support a new paradigm for direct Wnt target gene co-regulation with context-specific mechanisms that will inform future studies of embryonic development and more widely stem cell-mediated homeostasis and human disease.

KW - Ctnnb1

KW - β-catenin

KW - Wnt signaling

KW - Zygotic Gene Activation

KW - Mid-Blastula Transition

KW - Axis induction

KW - Biological Sciences

KW - Molecular Biology

KW - Developmental Biology

KW - TRANSCRIPTION FACTORS

KW - SIGNALING PATHWAYS

KW - INDUCTION

KW - BETA-CATENIN

KW - MESODERM

KW - DNA

KW - SIAMOIS

KW - WNT

KW - EXPRESSION

KW - BINDING

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U2 - 10.1016/j.isci.2020.101314

DO - 10.1016/j.isci.2020.101314

M3 - Article

C2 - 32650116

VL - 23

JO - iScience

JF - iScience

IS - 7

M1 - 101314

ER -

Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development

Abstract

Bibliographical note

Keywords

UN SDGs

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Stefan Hoppler

Centre for Genome-Enabled Biology and Medicine

Cite this

Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Profiles

Stefan Hoppler

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Centre for Genome-Enabled Biology and Medicine

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