Molecular analysis of G+C-rich upstream sequences regulating transcription of the human carbonic anhydrase II gene.

Abstract

The upstream promoter sequences of the human carbonic anhydrase II (CA H) gene have been studied by 5' deletion analysis. Promoter activity was assayed by transfection and chloramphenicol acetyltransferase assay in both human HeLg cells and murine L cells. This investigation showed that the CA H promoter is comparable in activity to that of the simian virus 40 early-region promoter and enhancer and that the CA II upstream sequences exert a different pattern of control in the two cell lines.The analysis of gene regulation, both in general and at the tissue-specific level, requires a well-characterized gene system. The carbonic anhydrase (CA) isozyme system is well suited for such an analysis, as it has been extensively studied at both the biochemical and molecular level (6, 9). The wide distribution of the CA II isozyme lends itself to particularly interesting aspects of differential gene control, as CA II is found in almost all mammalian tissues, but it is differentially expressed in the cells of these tissues (7). The nucleotide sequences of the 5' regions of the CA II genes of humans and mice show a high degree of homology from 200 bases 5' of -550 G+C content and nine CCGCCC or GGGCGG boxes) and highly regulated genes (TATA box, P-globin-like tandem repeats, and limited cell-type expression) in the human CA II gene presents the possibility that this is an intermediate-type promoter (2) and may display unique regulatory mechanisms.The nucleotide sequence of the promoter to exon 1 of the human CA gene is shown in Fig. 1. This region is extremely G+C-rich and contains a high number of transcriptional control elements which have previously been characterized in other systems. First, a TATA box (TATAAAA) is located -500ACCCGCtTGTCc-CAGGCCGGGGACACCAGAGACTGAGCCCTTGCGCGCTGGAGACCCGGCGCGGGTGCdiaCfGAGnGCACCGGGGCCAAGAGACAG

Carbonic anhydrase II (CA II) deficiency in Maghrebian patients: evidence for founder effect and genomic recombination at the CA II locus

“…The apparently high frequency of this event suggests the existence of a hot spot for gene conversion or recombination upstream of the CA II gene. Presumably, the existence of DNA sequences that could serve as a recombination signal (Venta et al 1985;Shapiro et al 1987) upstream of the CA II gene would favor the recombination or gene conversion alternative and offers a structural basis to explain the elevated recombination frequency.…”

Transcriptional regulation of carbonic anhydrase II by retinoic acid in the human pacreatic tumor cell line DANG

“…Therefore a decrease in CA lI gene transcription is predominantely if not exclusively, responsible for the inhibition of CA II expression in DANG cells. Although the promotor region of the human CA II gene has been cloned and sequenced [22], very few physiological or pharmacological substances have been identified that regulate CA II gene expression. In this context it is of interest, that another member of the steroid hormone superfamily, 1,25-dihydroxyvitamin D 3, exerts opposite effects on CA II gene expression in an osteoclast cell line, characteri sed by an increase of CA I I gene expression [l 3].…”

Novel transcripts of carbonic anhydrase II in mouse and human testis

“…Alternative transcription initiation sites were found in different testis clones (Figure 1). The additional 5ЈUTR sequence contains the 'TATA box', a putative CCAAT box (CCACT), three tandem-repeat elements located 15 pairs upstream from the CCAAT box, GϩC-rich boxes and similar sequences to those found in the 5Ј region of the human carbonic anhydrase II gene that have been reported as important for regulation of transcription (Venta et al, 1985;Shapiro et al, 1987;Marino, 1993). Computer analysis shows a prediction of a possible secondary structure (Figure 2).…”