Abstract
Embryonic development entails a well defined temporal and spatial programme of gene expression, which may be influenced by active chromosomal domains. These chromosomal domains can be detected using transgenes which integrate randomly throughout the genome, as their expression can be affected by chromosomal position1–3. Position effects are probably exerted most strongly on transgenes that do not contain strong promoters, enhancers or other modulating sequences. Here we have systematically explored position effects using a transgene with the weak herpes-simplex-virus thymidine-kinase promoter, linked to the readily visualized lacZ indicator gene (HSV-TK-lacZ). Each transgenic fetus with detectable expression displayed a unique lacZ staining pattern. Thus expression of this construct is apparently dictated entirely by its chromosomal position, without any construct specificity. Furthermore the transgene is faithfully transmitted to subsequent generations, allowing for systematic mapping of changes in expression during development and in adult life. These results demonstrate that transgenes can indeed be powerful tools to probe the genome for active chromosomal regions, with the potential for identifying endogenous genes involved in organogenesis and pattern formation.
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References
Palmiter, R. D. & Brinster, R. L. A. Rev. Genet. 20, 465–499 (1986).
Jaenisch, R. et al. Cell 24, 510–529 (1981).
Lacy, E., Roberts, S., Evans, E. P., Burtenshaw, M. D. & Costantini, F. D. Cell 34, 343–358 (1983).
Wagner, M. J., Sharp, J. A. & Summers, W. C. Proc. natn. Acad. Sci. U.S.A. 78, 1441–1445 (1981).
Hall, C., Jacob, P., Ringold, G. & Frank, L. J. molec. appl. Genet. 2, 101–109 (1983).
Wagner, E. F., Stewart, T. A. & Mintz, B. Proc. natn. Acad. Sci. U.S.A. 78, 5016–5020 (1981).
Brinster, R. L., Chen, H. Y., Warren, R., Sarthy, A. & Palmiter, R. D. Nature 296, 39–42 (1982).
Butner, K. & Lo, C. W. Molec. Cell Biol. 6, 4440–4449 (1986).
Sanes, J. R., Rubenstein, J. L. R. & Nicolas, J-F. EMBO J. 5, 3133–3142 (1986).
Turner, D. L. & Cepko, C. L. Nature 328, 131–136 (1987).
Goring, D. R., Rossant, J., Clapoff, S., Breitman, M. L. & Tsui, L. C. Science 235, 456–457 (1987).
Allen, N. D., Barton, S. C., Surani, M. A. H. & Reik, W. in Mammalian Development—A Practical Approach (ed. Monk, M.) 217–233 (IRL Press, Oxford, 1987).
Stewart, C. L., Schuetze, S., Vanek, M. & Wagner, E. F. EMBO J. 6, 383–388 (1987).
Rohdewohld, H., Weiher, H., Reik, W., Jaenisch, R. & Breindl, M. J. Virol. 61, 336–343 (1987).
Swanson, L. W. et al. Nature 317, 363–366 (1985).
Low, M. J. et al. Science 231, 1002–1024 (1987).
Das, O. P. & Massing, J. W. Molec. Cell. Biol. 7, 4490–4497 (1987).
Soriano, P., Cone, R., Mulligan, R. & Jaenisch, R. Science 234, 1409–1413 (1986).
Shani, M. Molec. Cell Biol. 6, 2624–2631 (1986).
Jahner, D. & Jaenisch, R. Molec. Cell Biol. 5, 2212–2220 (1985).
Sorge, J., Cutting, A., Erdman, V. & Gautsch, J. Proc. natn. Acad. Sci. U.S.A. 81, 6627–6631 (1984).
Barklis, E., Mulligan, R. & Jaenisch, R. Cell 47, 391–399 (1986).
Taketo, M. & Tanaka, M. Proc. natn. Acad. Sci. U.S.A. 84, 3748–3752 (1987).
Hamada, H. Molec. Cell Biol. 6, 4179–4184 (1986).
Hamada, H. Molec. Cell Biol. 6, 4185–4194 (1986).
Forrester, W. C., Takegawa, S., Papayannopoulou, T., Stamatoyannopoulos, G. & Groudine, M. Nucleic Acid Res. 15, 10159–10177 (1987).
Grosveld, F., van Assendelft, G. B., Greaves, D. R. & Kollias, G. Cell 51, 975–985 (1987).
Wilkie, T. M., Brinster, R. L. & Palmiter, R. D. Devl Biol. 118, 9–18 (1986).
O'Kane, C. J. & Gehring, W. J. Proc. natn. Acad. Sci. U.S.A. 84, 9123–9127 (1987).
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Alien, N., Cran, D., Barton, S. et al. Transgenes as probes for active chromosomal domains in mouse development. Nature 333, 852–855 (1988). https://doi.org/10.1038/333852a0
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DOI: https://doi.org/10.1038/333852a0
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