EFFECT OF TELOMERE LENGTH ON TELOMERIC GENE-EXPRESSION

Telomeres gradually shorten as human somatic cells divide and a correl ation has been observed between the average telomere length and cell s enescence. It has been proposed that the genes responsible for cell se nescence are located near the telomere and are activated when telomere length reaches a critical point. This is consistent with evidence fro m Saccharomyces cerevisiae, in which genes are regulated differently d epending on their distance from the telomere. We investigated the poss ibility that differential gene expression is conferred by telomere len gth in human cells. A plasmid containing the neomycin phosphotransfera se (neo) gene was transfected into the SV40-transformed human fibrobla st cell line LW217. In one transfectant the plasmid was integrated at the telomere of chromosome 13. Subclones of this cell line that had va rious lengths of telomeric repeat sequences on the end of this chromos ome were isolated. No effect on neo gene expression was found when the length of the telomere varied between 25 and 0.5 kb, as demonstrated by colony forming ability, growth rates and RNA blot analysis. these r esults therefore suggest that putative chromatin structural difference s conferred by telomere length do not affect the expression of genes l ocated near telomeres.