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XB-ART-53106
Development January 1, 2017; 144 (7): 1283-1295.

Genomic integration of Wnt/β-catenin and BMP/Smad1 signaling coordinates foregut and hindgut transcriptional programs.

Stevens ML , Chaturvedi P , Rankin SA , Macdonald M , Jagannathan S , Yukawa M , Barski A , Zorn AM .


Abstract
Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how these signals are interpreted in the genome is poorly understood. Here we identified the transcriptomes of Xenopus foregut and hindgut progenitors, which are conserved with mammals. Using RNA-seq and ChIP-seq we show that BMP/Smad1 regulates dorsal-ventral gene expression in both the endoderm and mesoderm, whereas Wnt/β-catenin acts as a genome-wide toggle between foregut and hindgut programs. Unexpectedly, β-catenin and Smad1 binding were associated with both transcriptional activation and repression, with Wnt-repressed genes often lacking canonical Tcf DNA binding motifs, suggesting a novel mode of direct repression. Combinatorial Wnt and BMP signaling was mediated by Smad1 and β-catenin co-occupying hundreds of cis-regulatory DNA elements, and by a crosstalk whereby Wnt negatively regulates BMP ligand expression in the foregut. These results extend our understanding of gastrointestinal organogenesis and of how Wnt and BMP might coordinate genomic responses in other contexts.

PubMed ID: 28219948
PMC ID: PMC5399627
Article link: Development
Grant support: [+]
Genes referenced: axin2 bmp2 bmp4 bmp7.1 bmp7.2 cdx2 cdx4 cebpa crebbp ctnnb1 darmin fetub foxc2 foxi4.1 fzd8 gata4 hand2 hhex hoxa6 hoxd10 hrg id2 id3 id4 kcnt1 mnx1 msx1 nkx2-1 nkx2-5 nr1h5 pdx1 sfrp2 sfrp5 smad1 sox2 sp5 spib szl tbx1 ventx1.1 ventx2.1 ventx2.2 wnt5a wnt5b wnt8b
Antibodies: Ctnnb1 Ab12 Smad1 Ab2 ep300 Ab1

GEO Series:
   GSE87652: NCBI
   GSE87653: Xenbase,  NCBI
   GSE87654: NCBI


Article Images: [+] show captions
References:
Akkers, 2012, Pubmed, Xenbase [+]


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