Transcriptional activation of Carbonic Anhydrase III (CAIII) mediated by SP1

Abstract

Many physiological and pathological processes require the expression and control of CAIII. Although the CAIII promoter has not been fully characterized, promoters for other carbonic anhydrase genes in humans have. In this research, we for the first time located and described the human Carbonic anhydrase III gene promoter region. Progressive deletion analysis of the 5′-flanking region of the CAIII gene showed that the CAIII core promoter is mainly restricted to a minimum region of 129 bp. The CAIII gene promoter was discovered to include additional potential binding sites for transcriptional factors including C/EBP and NF-B despite lacking the standard TATA box, according to an investigation of transcriptional factor binding. Furthermore, site-directed mutagenesis assay showed that the proximal Sp1 binding site is required for the essential core promoter activity of the CAIII gene. It was also shown that the CAIII gene was up-regulated by SP1 at the mRNA and protein levels, and this effect was also observed in deletion promoter constructs. Our current study will shed light on further studies on the mechanism that regulates the expression of this important gene.