title: Human muscle carbonic anhydrase: gene structure and DNA methylation patterns in fetal and adult tissues.
abstract: We report the isolation and analysis of genomic clones comprising the entire gene coding for the human muscle carbonic anhydrase, CAIII. The gene spans 10.3 kb and has a seven-exon/six-intron structure. A noncanonical TATA box, a CCAAT motif, and two CCGCCC elements are present in the sequences upstream of exon 1. Although the expression of CAIII shows strict tissue specificity, the gene exhibits a number of features normally associated with housekeeping enzymes. For example, there is 48% homology with a 25-bp consensus sequence between the TATA box and the cap site and there is a CpG-rich island spanning a 469-bp sequence near to the origin of transcription. Methylation studies suggest that some CCGG sites clustered in the CpG-rich island are undermethylated in DNA from fetal and adult muscle and in other tissues irrespective of CAIII expression. In contrast, several nonclustered CCGG sites show a methylation pattern that correlates with gene expression. However DNA from differentiated type II adult muscle fibers is undermethylated at these sites even though CAIII is not expressed.
authors.affiliation: Human Biochemical Genetics Unit, Galton Laboratory, University College London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Lloyd
authors.forename: C
authors.initials: C
authors.lastname: Brownson
authors.forename: S
authors.initials: S
authors.lastname: Tweedie
authors.forename: J
authors.initials: J
authors.lastname: Charlton
authors.forename: Y H
authors.initials: YH
authors.lastname: Edwards
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002256:Carbonic Anhydrases / Q000235:genetics*; D004262:DNA Restriction Enzymes; D005091:Exons; D005333:Fetus; D005796:Genes; D006801:Humans; D007438:Introns; D008745:Methylation; D008969:Molecular Sequence Data; D009132:Muscles / Q000196:embryology / Q000201:enzymology*; D011401:Promoter Regions, Genetic
chemical_list: D004262:DNA Restriction Enzymes; D002256:Carbonic Anhydrases