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A Core Response to the CDX2 Homeoprotein During Development and in Pathologies
Victor Gourain1, Isabelle Duluc2, Claire Domon-Dell2
1Karlsruhe Institute of Technology, Institute of Biological and Chemical Systems, Karlsruhe, Germany.
Abstract:
Whether a gene involved in distinct tissue or cell functions exerts a core of common molecular activities is a relevant topic in evolutionary, developmental, and pathological perspectives. Here, we addressed this question by focusing on the transcription factor and regulator of chromatin accessibility encoded by the Cdx2 homeobox gene that plays important functions during embryonic development and in adult diseases. By integrating RNAseq data in mouse embryogenesis, we unveiled a core set of common genes whose expression is responsive to the CDX2 homeoprotein during trophectoderm formation, posterior body elongation and intestinal specification. ChIPseq data analysis also identified a set of common chromosomal regions targeted by CDX2 at these three developmental steps. The transcriptional core set of genes was then validated with transgenic mouse models of loss or gain of function of Cdx2. Finally, based on human cancer data, we highlight the relevance of these results by displaying a significant number of human orthologous genes to the core set of mouse CDX2-responsive genes exhibiting an altered expression along with CDX2 in human malignancies.
Insights
The study identified a core set of genes regulated by the CDX2 homeobox gene during mouse embryonic development. These findings are relevant to human diseases, showing altered expression in cancers.
Area of Science:
- Developmental Biology
- Genetics
- Cancer Research
Background:
- The transcription factor CDX2 is crucial for embryonic development and adult diseases.
- Understanding conserved gene functions across different cellular contexts is vital.
Purpose of the Study:
- To investigate if the CDX2 homeobox gene, involved in various functions, shares a core set of molecular activities.
- To identify common genes and chromosomal regions targeted by CDX2 during distinct developmental stages.
Main Methods:
- Integration of RNA sequencing (RNAseq) and Chromatin Immunoprecipitation sequencing (ChIPseq) data from mouse embryogenesis.
- Validation using transgenic mouse models with altered CDX2 function.
- Analysis of human cancer datasets for orthologous gene expression.
Main Results:
- A core set of CDX2-responsive genes was identified during trophectoderm formation, posterior body elongation, and intestinal specification.
- Common chromosomal regions targeted by CDX2 were found across these developmental steps.
- A significant overlap was observed between mouse CDX2-responsive genes and human genes with altered expression in malignancies.
Conclusions:
- CDX2 homeoprotein orchestrates a conserved transcriptional program during key embryonic developmental events.
- The identified CDX2-regulated gene network is relevant to human cancers, indicating conserved roles in disease.
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