Role of the Snail family of transcription factors in human Disc large transcriptional regulation

CAVATORTA ANA LAURA, BUGNON VALDANO MARINA, GIRI ADRIANA, LAWRENCE BANKS AND GARDIOL DANIELA

Villa Carlos Paz

Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).; 2008

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

A number of studies have demonstrated the involvement of human Disc large (DLG1) oncosuppressor in the control of both cell polarity and maintenance of tissue architecture. However, the mechanisms controlling DLG1 transcription are poorly understood. This is relevant since DLG1 is lost in many tumours during the later stages of malignant progression. We cloned and functionally characterized the DLG1 promoter region. We found, within the DLG1 promoter sequences, E-boxes consensus binding sites for the Snail transcription factors. Snail proteins are involved in the epithelial–mesenchymal transition, in the repression of epithelial markers, and are up-regulated in a number of tumors. Snai1 and Snai2 factors repress the transcriptional activity of the DLG1 promoter and down-regulate DLG1 endogenous levels. Ectopically expressed and endogenous Snail proteins bind to the native DLG1 promoter as ascertained by Chromatin immunoprecipitation assays. These interactions depend on the integrity of the E-boxes present in the DLG1 promoter sequences. These data suggest a role for Snail transcription factors in the control of DLG1 expression and provide a basis for understanding the transcriptional regulation of DLG1. Analysis of the correlation between DLG1 and Snail protein expression in tumour biopsies, by immunohistochemistry, are currently being performed.