Gene ecology: Acis-acting gene-to-gene interaction due to the spatial arrangement of genes in chromosomes affects neighbouring transfected c-H-ras expression (original) (raw)

Abstract

A_cis_-acting interference between gene activities, which occurs when two genes lie on the same DNA strand and have an Intergenic distance less than a defined length, was previously deduced when chromo-somal organizations of various higher eukaryote nuclear genes in clusters were compared. In order to investigate such an interference due to arrangement of genes along chromosomes, we have isolated a few cell lines which possessed (i) human mutated c-H-ras fused with the mouse mammary tumour virus long terminal repeat and (ii) the_E. coli_ xanthine-guanine phosphoribosyltransferase (gpt) gene with the SV40 promoter, on the same or on different DNA strands, separated by a short intergenic distance or unlinked. Since the cancerous phenotype of a cell can be readily identified due to c-H-ras expression, we examined in these cell lines whether continuous c-H-ras expression, induced by dexamethasone, is disturbed through a_cis_-acting gene-to-gene interaction when the expression of the neighbouring_gpt_ gene is enforced and as a result, the cancerous state of a cell is converted to the ‘normal’ state. The enforced expression of the neighbouring_gpt_ gene was shown to alter c-H-ras expression, and thus reversible conversion of a cell between cancerous and normal states occurred only when the cell possessed an optimum number of the gene pair, in which both c-H-ras and the_gpt_ gene were on the same DNA strand. This implies that the spatial arrangement of genes in chromosomes plays an important role in the regulation of gene expression in a cluster.

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Authors and Affiliations

1. Research School of Biological Sciences, The Australian National University, PO Box 475, 2601, Canberra, ACT, Australia
   H. Naora, Z. Z. Xu, K. Miyahara & H. Liszczynsky
2. Shigei Medical Research Institute, 701-02, Okayama, Japan
   S. Seno

Authors

1. H. Naora
2. Z. Z. Xu
3. K. Miyahara
4. H. Liszczynsky
5. S. Seno

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Naora, H., Xu, Z.Z., Miyahara, K. et al. Gene ecology: A_cis_-acting gene-to-gene interaction due to the spatial arrangement of genes in chromosomes affects neighbouring transfected c-H-ras expression.Chromosome Res 2, 171–183 (1994). https://doi.org/10.1007/BF01553317

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• Received: 19 October 1993
• Revised: 13 December 1993
• Accepted: 15 December 1993
• Issue date: May 1994
• DOI: https://doi.org/10.1007/BF01553317

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