Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 155-165 |
| Number of pages | 11 |
| Journal | Genomics |
| Volume | 38 |
| Issue number | 2 |
| DOIs | |
| State | Published - Dec 1 1996 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
Cite this
Human glycogen debranching enzyme gene (AGL) : Complete structural organization and characterization of the 5' flanking region. / Bao, Yong; Dawson, Thomas L.; Chen, Yuan Tsong.
In: Genomics, Vol. 38, No. 2, 01.12.1996, p. 155-165.Research output: Contribution to journal › Article
}
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
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.
UR - http://www.scopus.com/inward/record.url?scp=0030447828&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030447828&partnerID=8YFLogxK
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 -