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: [+]
P30 DK078392 NIDDK NIH HHS , R01 DK070858 NIDDK NIH HHS , R01 HL114898 NHLBI NIH HHS , T32 HL007752 NHLBI NIH HHS , DP2 GM119134 NIGMS NIH HHS , UL1 TR001425 NCATS NIH HHS
Species referenced: Xenopus laevis
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: Xenbase, NCBI
Article Images: [+] show captions
References [+] :
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Xuan, Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis. 2012, Pubmed
Zhang, Different thresholds of Wnt-Frizzled 7 signaling coordinate proliferation, morphogenesis and fate of endoderm progenitor cells. 2013, Pubmed , Xenbase
Zhang, Model-based analysis of ChIP-Seq (MACS). 2008, Pubmed
Zorn, Vertebrate endoderm development and organ formation. 2009, Pubmed , Xenbase
Benahmed, Multiple regulatory regions control the complex expression pattern of the mouse Cdx2 homeobox gene. 2008, Pubmed
Benchabane, GATA- and Smad1-dependent enhancers in the Smad7 gene differentially interpret bone morphogenetic protein concentrations. 2003, Pubmed
Blitz, Finding partners: how BMPs select their targets. 2009, Pubmed
Blythe, beta-Catenin primes organizer gene expression by recruiting a histone H3 arginine 8 methyltransferase, Prmt2. 2010, Pubmed , Xenbase
Blythe, Chromatin immunoprecipitation in early Xenopus laevis embryos. 2009, Pubmed , Xenbase
Brown, The cardiac determination factor, Nkx2-5, is activated by mutual cofactors GATA-4 and Smad1/4 via a novel upstream enhancer. 2004, Pubmed
Cadigan, TCF/LEFs and Wnt signaling in the nucleus. 2012, Pubmed
Chalmers, The Xenopus tadpole gut: fate maps and morphogenetic movements. 2000, Pubmed , Xenbase
De Robertis, Spemann's organizer and the self-regulation of embryonic fields. 2009, Pubmed , Xenbase
Ding, Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling. 2000, Pubmed
Estarás, SMADs and YAP compete to control elongation of β-catenin:LEF-1-recruited RNAPII during hESC differentiation. 2015, Pubmed
Gaarenstroom, TGF-β signaling to chromatin: how Smads regulate transcription during self-renewal and differentiation. 2014, Pubmed
Gaunt, Vertebrate caudal gene expression gradients investigated by use of chick cdx-A/lacZ and mouse cdx-1/lacZ reporters in transgenic mouse embryos: evidence for an intron enhancer. 2003, Pubmed
Gibb, sfrp1 promotes cardiomyocyte differentiation in Xenopus via negative-feedback regulation of Wnt signalling. 2013, Pubmed , Xenbase
Green, Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells. 2011, Pubmed
Gupta, Developmental enhancers are marked independently of zygotic Nodal signals in Xenopus. 2014, Pubmed , Xenbase
Haworth, GATA4 and GATA5 are essential for heart and liver development in Xenopus embryos. 2008, Pubmed , Xenbase
Hoppler, BMP-2/-4 and Wnt-8 cooperatively pattern the Xenopus mesoderm. 1998, Pubmed , Xenbase
Itasaki, Crosstalk between Wnt and bone morphogenic protein signaling: a turbulent relationship. 2009, Pubmed
Jamora, Links between signal transduction, transcription and adhesion in epithelial bud development. 2003, Pubmed
Karaulanov, Transcriptional regulation of BMP4 synexpression in transgenic Xenopus. 2004, Pubmed , Xenbase
Kartashov, BioWardrobe: an integrated platform for analysis of epigenomics and transcriptomics data. 2015, Pubmed
Kenny, Sizzled-tolloid interactions maintain foregut progenitors by regulating fibronectin-dependent BMP signaling. 2012, Pubmed , Xenbase
Kim, Chromatin and transcriptional signatures for Nodal signaling during endoderm formation in hESCs. 2011, Pubmed
Kim, Smad-dependent recruitment of a histone deacetylase/Sin3A complex modulates the bone morphogenetic protein-dependent transcriptional repressor activity of Nkx3.2. 2003, Pubmed
Kjolby, Genome-wide identification of Wnt/β-catenin transcriptional targets during Xenopus gastrulation. 2016, Pubmed , Xenbase
Klaus, Developmental signaling in myocardial progenitor cells: a comprehensive view of Bmp- and Wnt/beta-catenin signaling. 2009, Pubmed
Kormish, Interactions between SOX factors and Wnt/beta-catenin signaling in development and disease. 2009, Pubmed
Lancaster, Organogenesis in a dish: modeling development and disease using organoid technologies. 2014, Pubmed
Langmead, Fast gapped-read alignment with Bowtie 2. 2012, Pubmed
Li, Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and noncanonical Wnt11 signaling. 2008, Pubmed , Xenbase
Li, RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. 2011, Pubmed
Lien, Cardiac-specific activity of an Nkx2-5 enhancer requires an evolutionarily conserved Smad binding site. 2002, Pubmed , Xenbase
Lin, Requirement for Wnt and FGF signaling in Xenopus tadpole tail regeneration. 2008, Pubmed , Xenbase
Loh, Efficient endoderm induction from human pluripotent stem cells by logically directing signals controlling lineage bifurcations. 2014, Pubmed
Loh, Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types. 2016, Pubmed
Marty, Schnurri mediates Dpp-dependent repression of brinker transcription. 2000, Pubmed , Xenbase
McLin, Repression of Wnt/beta-catenin signaling in the anterior endoderm is essential for liver and pancreas development. 2007, Pubmed , Xenbase
Nakamura, Tissue- and stage-specific Wnt target gene expression is controlled subsequent to β-catenin recruitment to cis-regulatory modules. 2016, Pubmed , Xenbase
Olson, Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination. 2006, Pubmed
Rankin, A gene regulatory network controlling hhex transcription in the anterior endoderm of the organizer. 2011, Pubmed , Xenbase
Risso, Normalization of RNA-seq data using factor analysis of control genes or samples. 2014, Pubmed
Rossi, Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm. 2001, Pubmed
Schohl, Beta-catenin, MAPK and Smad signaling during early Xenopus development. 2002, Pubmed , Xenbase
Session, Genome evolution in the allotetraploid frog Xenopus laevis. 2016, Pubmed , Xenbase
Sherwood, Wnt signaling specifies and patterns intestinal endoderm. 2011, Pubmed
Skalska, Chromatin signatures at Notch-regulated enhancers reveal large-scale changes in H3K56ac upon activation. 2015, Pubmed
Spence, Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. 2011, Pubmed , Xenbase
Theisen, Wingless directly represses DPP morphogen expression via an armadillo/TCF/Brinker complex. 2007, Pubmed
Trompouki, Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration. 2011, Pubmed
Tsankov, Transcription factor binding dynamics during human ES cell differentiation. 2015, Pubmed
Wang, Epigenetic priming of enhancers predicts developmental competence of hESC-derived endodermal lineage intermediates. 2015, Pubmed
Watanabe, Integrative ChIP-seq/microarray analysis identifies a CTNNB1 target signature enriched in intestinal stem cells and colon cancer. 2014, Pubmed
Wu, GSK3: a multifaceted kinase in Wnt signaling. 2010, Pubmed
Xuan, Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis. 2012, Pubmed
Zhang, Different thresholds of Wnt-Frizzled 7 signaling coordinate proliferation, morphogenesis and fate of endoderm progenitor cells. 2013, Pubmed , Xenbase
Zhang, Model-based analysis of ChIP-Seq (MACS). 2008, Pubmed
Zorn, Vertebrate endoderm development and organ formation. 2009, Pubmed , Xenbase