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.
Highlights
That evolution makes new out of old suggests the existence of shared properties between the functions of a given gene at its different times or sites of action
To address if there is a common set of genes responsive to the CDX2 transcription factor during its successive functions in mouse embryogenesis, we analyzed publicly available RNAseq data related to trophectoderm formation, posterior growth, and intestinal fate determination
These results demonstrate the existence of a core set of genes responsive to CDX2 during its successive functions in embryonic development
Summary
That evolution makes new out of old suggests the existence of shared properties between the functions of a given gene at its different times or sites of action. The homeobox gene encoding the CDX2 transcription factor allows addressing this assumption since it drives three major developmental processes in mammals. Cdx actively participates in axial posterior body growth at gastrulation through a convergent effect with T-Brachyury to maintain stemness properties of neuro-mesodermal axial progenitors and to sustain Fgf and Wnt signaling (van Rooijen et al, 2012; Amin et al, 2016). Cdx determines intestinal identity of the mid-/hindgut endoderm in embryos and allows identity maintenance of the adult gut epithelium by regulating the proliferation of stem/ progenitor cells and the differentiation of mature enterocytes (Gao et al, 2009; Verzi et al, 2010; Stringer et al, 2012). It binds distant chromatin regions to prevent epigenetic silencing and keep chromatin domains open and active (Saxena et al, 2017)
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