title: Human glycogen debranching enzyme gene (AGL): complete structural organization and characterization of the 5' flanking region.
abstract: Glycogen debranching enzyme (gene symbol, AGL) is a multifunctional enzyme acting as 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6-glucosidase in glycogen degradation. Genetic deficiency of AGL activity causes glycogen storage disease type III (GSD-III). To determine the molecular basis of GSD-III and elucidate the mechanisms for controlling tissue-specific gene expression, we report the isolation and structural organization of the human chromosomal AGL gene. The gene is 85 kb in length and is composed of 35 exons, encoding a 7.0-kb mRNA. The first 2 exons and 68 bp of exon 3 contain 5' untranslated region. Translation begins in exon 3, which encodes the first 27 amino acids of the AGL. Exons 4 to 35 encode the remaining 1505 amino acids. Among the 6 isoforms identified, the major isoform (isoform 1) starts with exon 1 and is widely expressed, including expression in both liver and muscle. Muscle-specific isoforms (2, 3, and 4) begin with exon 2. Isoforms 5 and 6 are minor isoforms that begin further within the gene. Reporter assays revealed that promoter region 1 (for isoform 1) was functional in liver (HepG2 cells), muscle (C2C12 cells), and ovary (Chinese hamster ovary cells), and promoter region 2 (for muscle-specific isoforms) was active only in muscle. These results suggest that the human AGL gene contains at least 2 promoter regions that confer differential expression of isoform mRNAs in a tissue-specific manner.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Bao
authors.forename: T L
authors.initials: TL
authors.lastname: Dawson
authors.forename: Y T
authors.initials: YT
authors.lastname: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D005796:Genes; D006004:Glycogen Debranching Enzyme System / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D006004:Glycogen Debranching Enzyme System; D012333:RNA, Messenger