Skip to main content
Log in

Structure of the mouse 3-Methyladenine DNA Glycosylase gene and exact localization upstream of the α-globin gene cluster on Chromosome 11

  • Original Contributions
  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

In this paper we describe the genomic organization of the mouse 3-Methyladenine DNA Glycosylase (MPG) gene and localize three putative regulatory elements around this gene. The MPG gene plays a key role in the excision repair of methylated adenine residues and has been localized upstream of the α-globin gene cluster in human and mouse. The human MPG gene has been fully characterized, whereas up to now only the cDNA sequence of the mouse MPG gene had been published. Here, we describe a detailed restriction map, the intron/exon structure, the CpG-rich putative promoter sequence, and the exact localization of the mouse MPG gene with respect to the murine α-globin gene cluster. Our analysis reveals a remarkable different exon/intron structure of the mouse MPG gene compared with its human homolog. Two prominent DNase hypersensitive sites (HSS) were found 0.1 and 1.5 kb upstream of the coding sequence. In addition to these elements, an erythroid prominent HSS was mapped at the intron/exon boundary of the last exon. The characterization and localization of the MPG gene in mouse makes it now possible to carry out transgenic and gene targeting experiments and are essential to understand the control of gene expression of the MPG gene in particular and of the whole region in general.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bird A.P. (1986). CpG-rich islands and the function of DNA methylation. Nature 321, 209–213.

    Google Scholar 

  • Chakravarti, D., Ibeanu, G.C., Tano, K., Mitra, S. (1991). Cloning and expression in Escherichia coli of a human cDNA encoding the DNA repair protein N-methylpurine-DNA glycosylase. J. Biol. Chem. 266, 15710–15715.

    Google Scholar 

  • Dahr, V., Nandi, A., Schildkraut, C.L., Skoultchi, A.I. (1990). Erythroid-specific nuclease hypersensitive sites flanking the human β-globin domain. Mol. Cell. Biol. 10, 4324–4333.

    Google Scholar 

  • Dickerson, R.D., Geis, I. (1993). Phylogenetic trees and evolutionary rates. In Hemoglobin: Structure, Function, Evolution, and Pathology, (Menlo Park, Calif.: Benjamin/Cummings Publishing Company, Inc., pp. 86–96.

    Google Scholar 

  • Engelward, B.P., Boosalis, M.S., Chen, B.J., Deng, Z., Siciliano, J., Samson, L.D. (1983). Cloning and characterization of a mouse 3-methyladenine/7-methylguanine DNA glycosylase cDNA whose gene maps to chromosome 11. Carcinogenesis 14, 175–181.

    Google Scholar 

  • Gardiner-Garden, M., Frommer, M. (1987). CpG islands in vertebrate genomes. J. Mol. Biol. 196, 261–282.

    Google Scholar 

  • Gross, D.S., Garrard, W.T. (1988). Nuclease hypersensitive sites in chromatin. Annu. Rev. Biochem. 57, 159–197.

    Google Scholar 

  • Grosveld, F., Dillon, N., Higgs, D.R. (1993). The regulation of human globin gene expression. In The Haemogloinopathies (D.R. Higgs and D.J. Wheatherall, Eds) Vol 6, pp. 31–55, Bailliere's Clinical Haematology.

  • Jarman, A.P., Higgs, D.R. (1988). A new hypervariable marker for the human α-globin gene cluster. Am. J. Hum. Genet. 43, 249–256.

    Google Scholar 

  • Jarman, A.P., Nicholls, R.D., Wheatherall, D.J., Clegg, J.B., Higgs, D.R. (1986). Molecular characterization of a hypervariable region downstream of the human α-globin gene cluster. EMBO J. 5, 1857–1863.

    Google Scholar 

  • Jarman, A.P., Wood, W.G., Sharpe, J.A., Gourdon, G., Ayyub, H., Higgs, D.R. (1991). Characterization of the major regulatory element upstream of the human α-globin gene cluster. Mol. Cell. Biol. 11, 4679–4689.

    Google Scholar 

  • Kielman, M.F., Smits, R., Devi, T.S., Fodde, R., Bernini, L.F. (1993). Homology of a 130-kb region enclosing the α-locus controlling region, and two non-globin genes in human and mouse. Mamm. Genome 4, 314–323.

    Google Scholar 

  • Kielman, M.F., Smits, R., Bernini, L.F. (1994). Localization and characterization of the mouse α-globin locus control region. Genomics 21, 431–433.

    Google Scholar 

  • Krainer, A.R., Maniatis, T. (1988). RNA splicing. In Transcription and Splicing, B.D. Hames, D.M. Glover, eds. (Oxford: IRL Press), pp. 131–206.

    Google Scholar 

  • Leder, A., Weir, L., Leder, P. (1985). Characterization, expression, and evolution of the mouse embryonic ζ-globin gene. Mol. Cell. Biol. 5, 1025–1033.

    Google Scholar 

  • O'Conner, T.R., Laval, F. (1990). Isolation and structure of a cDNA expressing a mammalian 3-methyladenine-DNA glycosglase. EMBO J. 9:3337–3342.

    Google Scholar 

  • Orkin, S.H. (1990). Globin gene regulation and switching: circa 1990. Cell 63, 665–672.

    Google Scholar 

  • Robbins, J., Dilworth, S.M., Laskey, R.A., Dingwall, C. (1991). Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: Identification of a class of bipartite nuclear targeting sequence. Cell 64, 615–623.

    Google Scholar 

  • Samson, L., Derfler, B., Boosalis, M., Call, K. (1991). Cloning and characterization of a 3-methyladenine DNA glycosylase cDNA from human cells whose gene maps to chromosome 16. Proc. Natl. Acad. Sci. USA, 88, 9127–9131.

    Google Scholar 

  • Vickers, M.A., Vyas, P., Harris, P.C., Simmons, D.L., Higgs, D.R. (1993). Structure of the human 3-methyladenine DNA glycosylase gene and localization close to the 16p telomere. Proc. Natl. Acad. Sci. 90, 3437–3441.

    Google Scholar 

  • Vyas, P., Vickers, M.A., Simmons, D.L., Ayyub, H., Craddock, C.F., Higgs, D.R. (1992). Cis-acting sequences regulating expression of the human α-globin cluster lie within constitutively open chromatin. Cell 69, 781–793.

    Google Scholar 

  • Wilkie, A.O.M., Higgs, D.R., Rack, K.A., Buckle, V.J., Spurr, N.K., Fishel-Godsian, N., Ceccherini, I., Brown, W.R.A., Harris, P.C. (1991). Stable length polymorphism of up to 260 kb at the tip of the short arm of human chromosome 16. Cell 64, 595–606.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The nucleotide sequence data reported in this paper will be submitted to Genbank.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kielman, M.F., Smits, R. & Bernini, L.F. Structure of the mouse 3-Methyladenine DNA Glycosylase gene and exact localization upstream of the α-globin gene cluster on Chromosome 11. Mammalian Genome 6, 499–504 (1995). https://doi.org/10.1007/BF00356165

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00356165

Keywords

Navigation