Abstract
THE regulatory elements that determine the expression pattern of a number of eukaryotic genes expressed specifically in certain tissues have been defined and studied in detail. In general, however, the expression conferred by these elements on genes reintroduced into the genomes of cell lines and transgenic animals has turned out to be at a low level relative to that of endogenous genes, and influenced by the chromosomal site of insertion of the exogenous construct. We have previously shown that if regions flanking the human β-globin locus are introduced into the mouse genome along with the human β-globin gene, a level of expression comparable to that of endogenous genes can be achieved that is also independent of integration site1,2. We have now defined a dominant control region with these properties consisting of 6.5 kilobases of DNA encompassing erythroid cell-specific DNase I hypersensitive sites. The identification of such dominant control regions could have important applications in somatic gene therapy.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Grosveld, F., Blom van Assendelft, G., Greaves, D. R. & Kollias, G. Cell 51, 975–985 (1987).
Blom van Assendelft, G., Hanscombe, O., Grosveld, F. & Greaves, D. R. Cell 56, 969–977 (1989).
Tuan, D., Solomon, W., Li, Q. & London I. M. Proc. natn. Acad. Sci. U.S.A. 82, 6384–6388 (1985).
Forrester, W. C., Takegawa, S., Papayannopoulou, T., Stamatoyannopoulos, G. & Groudine, M. Nucleic Acids Res. 15, 10159–10177 (1987).
Marks, P. A. & Rifkind, R. A. A. Rev. Biochem. 47, 419–426 (1978).
Kollias, G., Hurst, J., deBoer, E. & Grosveld, F. Nucleic. Acids Res., 15, 5739–5747 (1987).
Behringer, R. R., Hammer, R. E., Brinster, R. L., Palmiter, R. D. & Townes, T. M. Proc. natn. Acad. Sci. U.S.A. 84, 7056–7060 (1987).
Trudel, M., Magram, J., Bruckner, C. & Costantini, F. Molec. cell. Biol. 7, 4024–4029 (1987).
Antoniou, M., deBoer, E., Habets, G. & Grosveld, F. EMBO J. 7, 377–384 (1988).
Banerji, J., Rusconi, S. & Schaffner, W. Cell 27, 299–300 (1981).
Dzierzak, E., Papayannopoulou, T. & Mulligan, R. Nature 331, 35–41 (1988).
Cone, R., Benarous, W., Baorto, D. & Mulligan, R. Molec. cell. Biol. 7, 887–897 (1987).
Bender, M., Miller, D. & Gelinas, R. Molec. cell. Biol. 8, 1725–1738 (1988).
Luzzatto, L. & Goodfellow, P. Nature. 337, 17–18 (1989).
Grosveld, F. et al. Nucleic. Acids Res. 10, 6715–6732 (1982).
Auffrey, C. & Rougeon, R. Eur. J. Biochem. 107, 303–314 (1980).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Talbot, D., Collis, P., Antoniou, M. et al. A dominant control region from the human β-globin locus conferring integration site-independent gene expression. Nature 338, 352–355 (1989). https://doi.org/10.1038/338352a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/338352a0
This article is cited by
-
Building regulatory landscapes reveals that an enhancer can recruit cohesin to create contact domains, engage CTCF sites and activate distant genes
Nature Structural & Molecular Biology (2022)
-
Supercharging BRD4 with NUT in carcinoma
Oncogene (2021)
-
Treating hemoglobinopathies using gene-correction approaches: promises and challenges
Human Genetics (2016)
-
Production of recombinant human proinsulin in the milk of transgenic mice
Scientific Reports (2014)
-
Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells
Nature Genetics (2010)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
