TY - JOUR
T1 - Human glycogen debranching enzyme gene (AGL)
T2 - Complete structural organization and characterization of the 5' flanking region
AU - Bao, Yong
AU - Dawson, Thomas L.
AU - Chen, Yuan Tsong
N1 - Funding Information:
This work was supported by National Institute of Health Grants DK39078 (to Y.T.C.) and M01-RR30 (National Center for Research Sources, General Clinical Research Center Program), and by the Muscular Dystrophy Association. We also thank Eugene Berkowitz and Sue Fenton for their technical expertise during the luciferase assays.
PY - 1996/12/1
Y1 - 1996/12/1
N2 - Glycogen debranching enzyme (gene symbol, AGL) is a multifunctional enzyme acting as 1, 4-α-D-glucan:1, 4-α-D-glucan 4-α-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.
AB - Glycogen debranching enzyme (gene symbol, AGL) is a multifunctional enzyme acting as 1, 4-α-D-glucan:1, 4-α-D-glucan 4-α-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.
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U2 - 10.1006/geno.1996.0611
DO - 10.1006/geno.1996.0611
M3 - Article
C2 - 8954797
AN - SCOPUS:0030447828
VL - 38
SP - 155
EP - 165
JO - Genomics
JF - Genomics
SN - 0888-7543
IS - 2
ER -