Regulation of the CA1, CA2 and CA3 genes.

Abstract

In this chapter we will describe what is known about the regulation of the carbonic anhydrase (CA) genes closely clustered on human chromosome 8 and mouse chromosome 3, CA1, CA2 and CA3.(Fig. 1). These genes encode the cytosolic proteins CAI, CAII and CAIII which show considerable homology in their primary structures but differences in the detail of their catalytic properties. For example CAII has a CO2 turnover number at least 100 fold greater than that of CAIII, while CAIII has been shown to possess a unique phosphatase activity and can efficiently dephosphorylate phosphotyrosine residues (Cabiscol and Levine, 1996). These three genes are also distinguished by their temporal and spatial patterns of expression and this is likely to have arisen by sequence divergence in their regulatory elements after gene duplication. The promoters of the CA2 and CA3 genes are both G + C rich and show some localized sequence homologies which signal a common ancestry for their promoters, however the CAI promoter is not G + C rich and shows no homology to those of CA2 and A3. The CA1 gene is inverted in its genomic orientation relative to the other two genes. An inversion event sometime in the genomic history of this gene cluster could have led to the aquisition of novel 5’ flanking sequence and discrete regulatory control. Open image in new window Fig. 1 Map of the carbonic anhydrase gene cluster (CA1, CA2, and CA3) on human chromosome 8 (8q22). Exons are indicated as blocks; transcription start sites determined by two promoters in CA1 and CA2, and one in CA3 are shown as arrows. The major sites of expression for each gene promoter are indicated below.