G·A·B·B·A

Cadherin genes have been for long recognized as key elements in several pathologies, from muscular dystrophy to cancer. The biologically hazardous impact of cadherin impairment is directly linked to the fundamental roles performed by cadherin genes, ranging from cell-cell adhesion to synapse formation and cell migration. However, few are the known underlying mechanisms to cadherin impairment. The documented mechanisms include gene mutation, allelic imbalance and promoter methylation.
The severe pathological consequences of cadherin impairment and the lack of clarifying regulatory mechanisms stress the relevance of new approaches to cadherin regulation. We have opted for an intronic focused approach in order to detect non-coding putatively regulatory new elements with relevance to the cadherin gene superfamily. Our focus on cadherin introns derived from previous studies, which revealed the presence of fundamental intronic-based regulatory elements within an intron of CDH1, without which the expression of the encoded protein E- cadherin was lost. Our study represents a global approach to the cadherin gene superfamily in particular to its introns. Rather than searching for a particular regulatory mechanism associated with a single cadherin gene, we aimed at obtaining data, which will empower the focus on the non-coding areas of cadherins.
We have analyzed cadherin intronic relevance using a combined approach of bioinformatics and wet lab tools. By readdressing cadherin genomic structure, we have shown that the total intron number is a solid measure for gene classification within the cadherin superfamily. This measure reflects very specific functional characteristics at the protein sequence level, as well as provides evidence for several cadherin superfamily members re-classification.
Using transcriptome analysis tools and the embryogenesis model, we have observed massive cadherin intronic derived transcription. Interestingly, we have observed transcriptionally active regions both embryogenesis stage specific as well as found throughout this biological process, regardless of the stage. This part of our study, given the broad approach undertook, has provided several hints into cadherin regulation: for example, we have uncovered several features of cadherin intronic transcription in association to annotated genomic features, such as repetitive elements. We pursued our study by focusing on a specific biological process and cell type. Again intronic transcription was massively present, putatively underlying novel alternative exons as well as non-coding regulatory elements. All the data generated as been placed freely available online (upon request) thus providing extra information for scientists working on cadherin genes and regulation.
In conclusion, we believe that our study has shown the deep impact that cadherin introns may have in the regulation of this superfamily of genes. Both by constituting an added layer to cadherin genes' classification or by providing novel exons and/or non-coding regulatory elements, cadherin introns are of extreme biological relevance, that should be more highly considered from now on.