Autonomous Activity of the Alternate Aldolase A Muscle Promoter is Maintained by a Sequestering Mechanism

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 1992 Jan 25

PMID 1741258

Citations 3

Authors

J K Stauffer

Affiliations

Soon will be listed here.

Abstract

The mouse aldolase A gene contains two closely-spaced alternate promoter/first exons. The more distal of the two, the M promoter, is muscle-specific while the 3' promoter, the H promoter, is expressed constitutively. Various segments from these promoter regions were linked to a reporter gene and used to transfect the myogenic cell line C2C12 and the hepatoma cell line BWTG3. A muscle-specific enhancer, MEN1, responsible for 80% of promoter M activity and containing 4 consensus MyoD binding sites was localized between -2578 to -2723 of the M promoter. Another muscle-specific enhancer and a restrictive element, MEN2/MSE, were found in the interval -1100 to -350. The MSE restrictive element was found to prohibit inappropriate up-regulation of the M promoter by selectively sequestering it from H promoter elements in both myoblasts and myotubes. Among the H promoter elements was found an enhancer, HEN, situated between -533 and -200 which did not function in myotubes. These studies also show that H promoter elements can act synergistically with a non-specific element, MAE, located between -350 and -130 of the M cap site greatly stimulating M promoter transcription in all cell types when the MSE restrictive element was absent. Through the analysis of interactions between these elements and the aldolase A and HSV-TK promoters we showed that neither the enhancers nor the promoter proximal sequences by themselves contain adequate information to reproduce the native pattern of aldolase A promoter modulation. Rather, the sequestering of the M promoter by the MSE restrictive element and the relative positioning and context of promoters M and H appear critical to the regulated expression of aldolase A.

Citing Articles

Independence and interdependence of the three human aldolase A promoters in transgenic mice.

Moch C, Kahn A, Daegelen D Gene Expr. 1996; 6(1):1-14.

PMID: 8931987 PMC: 6148263.

An opportunistic promoter sharing regulatory sequences with either a muscle-specific or a ubiquitous promoter in the human aldolase A gene.

Concordet J, Salminen M, Demignon J, Moch C, Maire P, Kahn A Mol Cell Biol. 1993; 13(1):9-17.

PMID: 8417365 PMC: 358879. DOI: 10.1128/mcb.13.1.9-17.1993.

Fast-muscle-specific expression of human aldolase A transgenes.

Salminen M, Maire P, Concordet J, Moch C, Porteu A, Kahn A Mol Cell Biol. 1994; 14(10):6797-808.

PMID: 7935397 PMC: 359210. DOI: 10.1128/mcb.14.10.6797-6808.1994.

References

Colbert M . The proximal promoter of the aldolase A gene remains active during myogenesis in vitro and muscle development in vivo. Dev Biol. 1992; 149(1):66-79. DOI: 10.1016/0012-1606(92)90264-h. View

Gahlmann R, Kedes L . Cloning, structural analysis, and expression of the human fast twitch skeletal muscle troponin C gene. J Biol Chem. 1990; 265(21):12520-8. View

Gautron S, Maire P, Hakim V, Kahn A . Regulation of the multiple promoters of the human aldolase A gene: response of its two ubiquitous promoters to agents promoting cell proliferation. Nucleic Acids Res. 1991; 19(4):767-74. PMC: 333709. DOI: 10.1093/nar/19.4.767. View

Wentworth B, Donoghue M, Engert J, BERGLUND E, Rosenthal N . Paired MyoD-binding sites regulate myosin light chain gene expression. Proc Natl Acad Sci U S A. 1991; 88(4):1242-6. PMC: 50993. DOI: 10.1073/pnas.88.4.1242. View

Lin H, Yutzey K, Konieczny S . Muscle-specific expression of the troponin I gene requires interactions between helix-loop-helix muscle regulatory factors and ubiquitous transcription factors. Mol Cell Biol. 1991; 11(1):267-80. PMC: 359617. DOI: 10.1128/mcb.11.1.267-280.1991. View

Lemaigre F, Durviaux S, Rousseau G . Identification of regulatory sequences and protein-binding sites in the liver-type promoter of a gene encoding 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. Mol Cell Biol. 1991; 11(2):1099-106. PMC: 359787. DOI: 10.1128/mcb.11.2.1099-1106.1991. View

Donoghue M, Ernst H, Wentworth B, Nadal-Ginard B, Rosenthal N . A muscle-specific enhancer is located at the 3' end of the myosin light-chain 1/3 gene locus. Genes Dev. 1988; 2(12B):1779-90. DOI: 10.1101/gad.2.12b.1779. View

Landschulz W, Johnson P, Adashi E, Graves B, McKnight S . Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev. 1988; 2(7):786-800. DOI: 10.1101/gad.2.7.786. View

Schreiber E, Schaffner W . Long-range activation of transcription by SV40 enhancer is affected by "inhibitory" or "permissive" DNA sequences between enhancer and promoter. Somat Cell Mol Genet. 1989; 15(6):591-603. DOI: 10.1007/BF01534920. View

10.

Proudfoot N . Transcriptional interference and termination between duplicated alpha-globin gene constructs suggests a novel mechanism for gene regulation. Nature. 1986; 322(6079):562-5. DOI: 10.1038/322562a0. View

11.

Mar J, Ordahl C . A conserved CATTCCT motif is required for skeletal muscle-specific activity of the cardiac troponin T gene promoter. Proc Natl Acad Sci U S A. 1988; 85(17):6404-8. PMC: 281980. DOI: 10.1073/pnas.85.17.6404. View

12.

Devlin B, Wefald F, Kraus W, Bernard T, Williams R . Identification of a muscle-specific enhancer within the 5'-flanking region of the human myoglobin gene. J Biol Chem. 1989; 264(23):13896-901. View

13.

Izzo P, Costanzo P, Lupo A, Rippa E, Salvatore F . In vivo activity of the most proximal promoter of the human aldolase A gene and analysis of transcriptional control elements. FEBS Lett. 1989; 257(1):75-80. DOI: 10.1016/0014-5793(89)81790-9. View

14.

Seed B, Sheen J . A simple phase-extraction assay for chloramphenicol acyltransferase activity. Gene. 1988; 67(2):271-7. DOI: 10.1016/0378-1119(88)90403-9. View

15.

Colbert M . Alternative promoter usage by aldolase A during in vitro myogenesis. Dev Biol. 1988; 130(1):392-6. DOI: 10.1016/0012-1606(88)90444-7. View

16.

Izzo P, Costanzo P, Lupo A, Rippa E, Paolella G, Salvatore F . Human aldolase A gene. Structural organization and tissue-specific expression by multiple promoters and alternate mRNA processing. Eur J Biochem. 1988; 174(4):569-78. DOI: 10.1111/j.1432-1033.1988.tb14136.x. View

17.

Sternberg E, Spizz G, Perry M, Olson E . A ras-dependent pathway abolishes activity of a muscle-specific enhancer upstream from the muscle creatine kinase gene. Mol Cell Biol. 1989; 9(2):594-601. PMC: 362636. DOI: 10.1128/mcb.9.2.594-601.1989. View

18.

Luckow B, Schutz G . CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987; 15(13):5490. PMC: 305985. DOI: 10.1093/nar/15.13.5490. View

19.

Joh K, Arai Y, Mukai T, Hori K . Expression of three mRNA species from a single rat aldolase A gene, differing in their 5' non-coding regions. J Mol Biol. 1986; 190(3):401-10. DOI: 10.1016/0022-2836(86)90011-2. View

20.

Maire P, Gautron S, Hakim V, Gregori C, Mennecier F, Kahn A . Characterization of three optional promoters in the 5' region of the human aldolase A gene. J Mol Biol. 1987; 197(3):425-38. DOI: 10.1016/0022-2836(87)90556-0. View