Abstract
THE transcriptional activity of genes that have randomly integrated into the genomes of transfected cells and transgenic organisms is in general unpredictable, varying with the chromosomal site of the insertion1–4. This effect of chromosomal position on gene expression may reflect the organization of chromosomes into topologically constrained loops5–8 and functional domains9–12. To assess the biological significance of these loop domains, the anchorage of DNA to the nuclear scaffold has been studied at specific gene loci8,13–20. We have previously defined cis-acting regions flanking the chicken lysozyme-gene domain that mediate the attachment of the chromatin to the nuclear scaffold. These 'A-elements' map to the 5′ and 3′ boundaries of the region of general DNase sensitivity in the active chromatin10,17,21,22, which contains the lysozyme gene and its cis-regulatory elements10,23–28. Here we report that when a reporter gene is flanked by 5′ A-elements from the lysozyme gene, its expression in stably transfected cells is significantly elevated and is independent of chromosomal position.
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
Grindley, T., Soriano, P. and Jaenisch, R. Trends Genet. 3, 162–166 (1987).
Brinster, R. L. et al. Cell 27, 223–231 (1981).
Kucherlapati, R. & Skoultchi, A. J. CRC Crit. Rev. Biochem. 16, 349–381 (1984).
Palmiter, R. D. & Brinster, R. L. Cell 41, 343–349 (1985).
Cook, P. R. & Brazell, I. A. J. Cell Sci. 22, 287–302 (1976).
Igo-Kemenes, T. & Zachau, H. G. Cold Spring Harb. Symp. quant. Biol. 42, 109–118 (1977).
Nelson, W. G., Pienta, K. J., Barrack, E. R. and Coffey, D. S. A. Rev. biophys. Chem. 15, 457–475 (1986).
Gasser, S. M. & Laemmli, U. K. Trends Genet. 3, 16–22 (1987).
Jackson, D. A. Trends biochem. Sci. 11, 249–252 (1986).
Sippel, A. E. et al. in Architecture of Eukaryotic Genes (ed. Kahl, G.) 355–369 (VCH, Weinheim, FRG, 1988).
Grosveld, F., Blom van Assendelft, G., Greaves, D. R. & Kollias, G. Cell 51, 975–985 (1987).
Talbot, D. et al. Nature 338, 352–355 (1989).
Mirkovitch, J., Mirault, M.-E. & Laemmli, U. K. Cell 39, 223–232 (1984).
Cockerill, P. N. & Garrard, W. T. Cell 44, 273–282 (1986).
Gasser, S. M. & Laemmli, U. K. Cell 46, 521–530 (1986).
Käs, E. & Chasin, L. A. J. molec. Biol. 198, 677–692 (1987).
Phi-Van, L. & Strätling, W. H. EMBO J. 7, 655–664 (1988).
Bode, J. & Maas, K. Biochemistry 27, 4706–4711 (1988).
Jarman, A. P. & Higgs, D. R. EMBO J. 7, 3337–3344 (1988).
Hofmann, J. F.-X., Laroche, T., Brand, A. H. & Gasser, S. M. Cell 57, 725–737 (1989).
Strätling, W. H., Dölle, A. & Sippel, A. E. Biochemistry 25, 495–502 (1986).
Jantzen, K., Fritton, H. P. & Igo-Kemenes, T. Nucleic Acids Res. 14, 6085–6099 (1986).
Fritton, H. P. et al. Biol. Chem. Hoppe-Seyler 368, 111–119 (1987).
Gross, D. S. & Garrard, W. T. Ann. Rev. Biochem. 57, 159–197 (1988).
Fritton, H. P. et al. Nature 311, 163–165 (1984).
Theisen, M., Stief, A. & Sippel, A. E. EMBO J. 5, 719–724 (1986).
Steiner, C., Muller, M., Baniahmad, A. & Renkawitz, R. Nucleic Acids Res. 15, 4163–4178 (1987).
Hecht, A., Berkenstam, A., Strömstedt, P.-E., Gustafsson, J.-A. & Sippel, A. E. EMBO J. 7, 2063–2073 (1988).
Canaani, D. & Berg, D. P. Proc. natn. Acad. Sci. U.S.A. 79, 5166–5170 (1982).
Grez, M. et al. Cell 25, 743–752 (1981).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stief, A., Winter, D., Strätling, W. et al. A nuclear DNA attachment element mediates elevated and position-independent gene activity. Nature 341, 343–345 (1989). https://doi.org/10.1038/341343a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/341343a0
This article is cited by
-
Nuclear matrix associated RNAs in posterior silk glands show developmental dynamics in Bombyx mori in 5th instar larvae
BMC Research Notes (2022)
-
CTCF mediates dosage- and sequence-context-dependent transcriptional insulation by forming local chromatin domains
Nature Genetics (2021)
-
Benefits of using genomic insulators flanking transgenes to increase expression and avoid positional effects
Scientific Reports (2019)
-
Sus scrofa matrix attachment region enhances expression of the PiggyBac system transfected into HEK293T cells
Biotechnology Letters (2016)
-
Silencing porcine genes significantly reduces human-anti-pig cytotoxicity profiles: an alternative to direct complement regulation
Transgenic Research (2016)
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.