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Genome-wide identification of Wnt/?-catenin transcriptional targets during Xenopus gastrulation.

ABSTRACT: The canonical Wnt/?-catenin signaling pathway plays multiple roles during Xenopus gastrulation, including posteriorization of the neural plate, patterning of the mesoderm, and induction of the neural crest. Wnt signaling stabilizes ?-catenin, which then activates target genes. However, few targets of this signaling pathway that mediate early developmental processes are known. Here we sought to identify transcriptional targets of the Wnt/?-catenin signaling pathway using a genome-wide approach. We selected putative targets using the criteria of reduced expression upon zygotic Wnt knockdown, ?-catenin binding within 50kb of the gene, and expression in tissues that receive Wnt signaling. Using these criteria, we found 21 novel direct transcriptional targets of Wnt/?-catenin signaling during gastrulation and in addition have identified putative regulatory elements for further characterization in future studies.

SUBMITTER: Kjolby RAS

PROVIDER: S-EPMC6288011 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Genome-wide identification of Wnt/β-catenin transcriptional targets during Xenopus gastrulation.

Kjolby Rachel A S RAS Harland Richard M RM

Developmental biology 20160416 2

The canonical Wnt/β-catenin signaling pathway plays multiple roles during Xenopus gastrulation, including posteriorization of the neural plate, patterning of the mesoderm, and induction of the neural crest. Wnt signaling stabilizes β-catenin, which then activates target genes. However, few targets of this signaling pathway that mediate early developmental processes are known. Here we sought to identify transcriptional targets of the Wnt/β-catenin signaling pathway using a genome-wide approach. W ...[more]

PMID: 27091726

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Project description:BackgroundThe importance of in silico predictions for understanding cellular processes is now widely accepted, and a variety of algorithms useful for studying different biological features have been designed. In particular, the prediction of cis regulatory modules in non-coding human genome regions represents a major challenge for understanding gene regulation in several diseases. Recently, studies of the Wnt signaling pathway revealed a connection with neurodegenerative diseases such as Alzheimer's. In this article, we construct a classification tool that uses the transcription factor binding site motifs composition of some gene promoters to identify new Wnt/beta-catenin pathway target genes potentially involved in brain diseases.ResultsIn this study, we propose 89 new Wnt/beta-catenin pathway target genes predicted in silico by using a method based on multiple Classification and Regression Tree (CART) analysis. We used as decision variables the presence of transcription factor binding site motifs in the upstream region of each gene. This prediction was validated by RT-qPCR in a sample of 9 genes. As expected, LEF1, a member of the T-cell factor/lymphoid enhancer-binding factor family (TCF/LEF1), was relevant for the classification algorithm and, remarkably, other factors related directly or indirectly to the inflammatory response and amyloidogenic processes also appeared to be relevant for the classification. Among the 89 new Wnt/beta-catenin pathway targets, we found a group expressed in brain tissue that could be involved in diverse responses to neurodegenerative diseases, like Alzheimer's disease (AD). These genes represent new candidates to protect cells against amyloid beta toxicity, in agreement with the proposed neuroprotective role of the Wnt signaling pathway.ConclusionsOur multiple CART strategy proved to be an effective tool to identify new Wnt/beta-catenin pathway targets based on the study of their regulatory regions in the human genome. In particular, several of these genes represent a new group of transcriptional dependent targets of the canonical Wnt pathway. The functions of these genes indicate that they are involved in pathophysiology related to Alzheimer's disease or other brain disorders.

Dataset Information

Genome-wide identification of Wnt/?-catenin transcriptional targets during Xenopus gastrulation.

Publications

Genome-wide identification of Wnt/β-catenin transcriptional targets during Xenopus gastrulation.

Similar Datasets

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