Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development
Summary: Although 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 id...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220305010 |
| _version_ | 1829112873858629632 |
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| author | Boni A. Afouda Yukio Nakamura Sophie Shaw Rebekah M. Charney Kitt D. Paraiso Ira L. Blitz Ken W.Y. Cho Stefan Hoppler |
| author_facet | Boni A. Afouda Yukio Nakamura Sophie Shaw Rebekah M. Charney Kitt D. Paraiso Ira L. Blitz Ken W.Y. Cho Stefan Hoppler |
| author_sort | Boni A. Afouda |
| collection | DOAJ |
| description | Summary: Although 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 feedforward 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. |
| first_indexed | 2024-12-12T15:24:43Z |
| format | Article |
| id | doaj.art-db113fb346e24e129dd2a39f7b2d443d |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-12T15:24:43Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-db113fb346e24e129dd2a39f7b2d443d2022-12-22T00:20:18ZengElsevieriScience2589-00422020-07-01237101314Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early DevelopmentBoni A. Afouda0Yukio Nakamura1Sophie Shaw2Rebekah M. Charney3Kitt D. Paraiso4Ira L. Blitz5Ken W.Y. Cho6Stefan Hoppler7Institute of Medical Sciences, Foresterhill Health Campus, University of Aberdeen, ABERDEEN AB25 2ZD Scotland, UKInstitute of Medical Sciences, Foresterhill Health Campus, University of Aberdeen, ABERDEEN AB25 2ZD Scotland, UKCentre for Genome Enabled Biology and Medicine, Old Aberdeen Campus, University of Aberdeen, ABERDEEN AB24 2FX Scotland, UKDepartment of Developmental and Cell Biology, School of Biological Sciences, University of California, Irvine, CA 92697, USADepartment of Developmental and Cell Biology, School of Biological Sciences, University of California, Irvine, CA 92697, USADepartment of Developmental and Cell Biology, School of Biological Sciences, University of California, Irvine, CA 92697, USADepartment of Developmental and Cell Biology, School of Biological Sciences, University of California, Irvine, CA 92697, USAInstitute of Medical Sciences, Foresterhill Health Campus, University of Aberdeen, ABERDEEN AB25 2ZD Scotland, UK; Corresponding authorSummary: Although 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 feedforward 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.http://www.sciencedirect.com/science/article/pii/S2589004220305010Biological SciencesMolecular BiologyDevelopmental Biology |
| spellingShingle | Boni A. Afouda Yukio Nakamura Sophie Shaw Rebekah M. Charney Kitt D. Paraiso Ira L. Blitz Ken W.Y. Cho Stefan Hoppler Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development iScience Biological Sciences Molecular Biology Developmental Biology |
| title | Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development |
| title_full | Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development |
| title_fullStr | Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development |
| title_full_unstemmed | Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development |
| title_short | Foxh1/Nodal Defines Context-Specific Direct Maternal Wnt/β-Catenin Target Gene Regulation in Early Development |
| title_sort | foxh1 nodal defines context specific direct maternal wnt β catenin target gene regulation in early development |
| topic | Biological Sciences Molecular Biology Developmental Biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220305010 |
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