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Genomic integration of Wnt/b-catenin and BMP/Smad1 coordinates the transcriptional program of foregut and hindgut progenitors

ABSTRACT: Genomic integration of Wnt/b-catenin and BMP/Smad1 coordinates the transcriptional program of foregut and hindgut progenitors

PROVIDER: PRJNA345481 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR4346390.fastq.gz	Fastqsanger.gz
	SRR4346400.fastq.gz	Fastqsanger.gz
	SRR4346410.fastq.gz	Fastqsanger.gz
	SRR4346420.fastq.gz	Fastqsanger.gz
	SRR4346430.fastq.gz	Fastqsanger.gz

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Genomic integration of Wnt/b-catenin and BMP/Smad1 coordinates the transcriptional program of foregut and hindgut progenitors [RNA-seq]

Project description:Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how they are integrated in the genome is poorly understood. Here we identified the Xenopus foregut and hindgut progenitor transcriptomes, which are largely 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/b-catenin acts as a genome-wide toggle between foregut and hindgut programs. In addition to b-catenin-Tcf promoting hindgut gene transcription, we unexpectedly observed Wnt-repressed foregut genes associated with b-catenin-binding to DNA lacking Tcf motifs, suggesting a novel direct repression. We define how BMP and Wnt signaling are integrated in the genome with Smad1 and β-catenin co-occupying DNA elements associated with hundreds of key regulatory genes. These results extend our understanding of GI organogenesis and how Wnt and BMP may coordinate genomic responses in other contexts.

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Genomic integration of Wnt/b-catenin and BMP/Smad1 coordinates the transcriptional program of foregut and hindgut progenitors [ChIP-seq]

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

Project description: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.

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Project description:The dorsoventral gradient of BMP signaling plays an essential role in embryonic patterning, with high BMP signal activating ventral-lateral mesoderm markers directly, and low BMP signal inducing neural tissues. The Zinc finger SWIM domain-containing protein 4 (zswim4) is expressed in the dorsal blastopore lip at the onset of Xenopus gastrula and then enriched at the forming neuroectoderm at mid-gastrula stages. Overexpression of zswim4 in Xenopus embryos causes inhibition of the anterior axis and shortened, curved body, and knockdown or knockout of zswim4 disturbed embryonic body axis formation and head development. The expression of ventral-lateral mesoderm marker genes was reduced after zswim4 overexpression and increased in embryos with zswim4 knockdown. Neural marker genes were repressed in zswim4 morphant. Mechanistically Zswim4 attenuates BMP signal through reducing protein stability of Smad1 in both Xenopus embryos and HEK293T cells. Zswim4 interacts with Smad1 and promotes ubiquitination of Smad1 in HEK293T cells. To identify the interaction partner of Zswim4 in regulating Smad1 stability, we performed SILAC based IP in HEK293T cells, and the precipitates were analyzed by Mass Spectrometry.

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Genomic integration of Wnt/b-catenin and BMP/Smad1 coordinates the transcriptional program of foregut and hindgut progenitors

Project description:This SuperSeries is composed of the SubSeries listed below.

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Expression data of human umbilical vein endothelial cells (HUVECs) treated with BMP-6 and BMP-9

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