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

iScience

Sophie Shaw¹  Kitt D. Paraiso²  Ira L. Blitz²  Rebekah M. Charney²  Ken W.Y. Cho²  Yukio Nakamura³  Stefan Hoppler³  Boni A. Afouda³ 

[1] Centre for Genome Enabled Biology and Medicine, Old Aberdeen Campus, University of Aberdeen, ABERDEEN AB24 2FX Scotland, UK;Department of Developmental and Cell Biology, School of Biological Sciences, University of California, Irvine, CA 92697, USA;Institute of Medical Sciences, Foresterhill Health Campus, University of Aberdeen, ABERDEEN AB25 2ZD Scotland, UK;

关键词: Biological Sciences;    Molecular Biology;    Developmental Biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown