Cloning and functional analysis of the promoter region of the human Disc large gene.
A number of studies have demonstrated the involvement of human Disc large (DLG1) in the control of both cell polarity and maintenance of tissue architecture. However, the mechanisms controlling DLG1 transcription are not fully understood. This is relevant since DLG1 is lost in many tumours during the later stages of malignant progression. Therefore, we performed the cloning and functional analysis of a genomic 5' flanking region of the DLG1 open reading frame with promoter activity. We analyzed the activity of a series of 5' deletion constructs of the DLG1 promoter and determined the minimal essential sequences that are required for promoter activity as well as cis-elements that regulate transcription. We found, within the DLG1 promoter sequences, consensus-binding sites for the Snail family of transcription factors that repress the expression of epithelial markers and are up-regulated in a variety of tumours. Snail transcription factors repress the transcriptional activity of the DLG1 promoter and, ectopically expressed Snail proteins bind to the native DLG1 promoter. 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.
Cavatorta
Ana Laura
AL
Area Virología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Instituto de Biología Molecular y Celular de Rosario-CONICET, Universidad Nacional de Rosario, Rosario, Argentina.
Giri
Adriana A
AA
Banks
Lawrence
L
Gardiol
Daniela
D
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D001483:Base Sequence; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D017931:DNA Primers; D000074288:Discs Large Homolog 1 Protein; D005784:Gene Amplification; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006801:Humans; D007668:Kidney; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016366:Open Reading Frames; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D017931:DNA Primers; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D012313:RNA