Transcriptional Analysis of the 5′-Noncoding Region of the Human Involucrin Gene (∗)

• Published in: The Journal of biological chemistry 1996-01, Vol.271 (1), p.512-520
• Main Authors: Lopez-Bayghen, Esther, Vega, Alfonso, Cadena, Adriana, Granados, Sonia E., Jave, Luis F., Gariglio, Patricio, Alvarez-Salas, Luis M.
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Cattle; Cells, Cultured; DNA; DNA Footprinting; DNA-Binding Proteins - metabolism; Enhancer Elements, Genetic; Erythroid-Specific DNA-Binding Factors; HeLa Cells; herpes simplex virus; Humans; Keratinocytes - metabolism; Molecular Sequence Data; Promoter Regions, Genetic; Protein Binding; Protein Precursors - genetics; Transcription Factor AP-1 - metabolism; Transcription Factors - metabolism; Transcription, Genetic; Transfection; YY1 Transcription Factor
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.1.512

Human involucrin whose gene transcription is directed by a 2456-nucleotide (nt) 5′-noncoding region is a structural component of the epithelial cornified layer. Transient transfection assays demonstrated that this region is transcriptionally active in multiplying keratinocytes and is enhanced by 2 mM CaCl2 treatment. Calcium-independent transcriptional activity and the interaction with the AP-1 transcriptional factor was located on the proximal part (nt −159 to −1) of the 5′-noncoding region. However, CaCl2 responsiveness was mapped to a distal 1185-nt fragment (nt −2456 to −1272). Moreover, this fragment potentiated the Herpes simplex thymidine kinase promoter in normal keratinocytes and is responsive to calcium treatment in a cell type-specific manner. Interestingly, the absence of a 491-nt fragment located between the two enhancer domains (nt −651 to −160) resulted in transcriptional activation in multiplying keratinocytes. This fragment interacts with AP-1 and the YY1 transcriptional silencer. It is concluded that human involucrin 5′-noncoding region contains at least three regulatory domains, a distal CaCl2-responsive enhancer, a putative transcriptional silencer (that interacts with AP-1 and YY1), and a proximal enhancer/promoter (that interacts with AP-1). Thus, this study demonstrates the presence of particular transcriptional factors can potentially regulate the human involucrin expression.