Journal Article

Telomere length and the expression of natural telomeric genes in human fibroblasts

Yi Ning, Jing-fan Xu, Yu Li, Liz Chavez, Harold C. Riethman, Peter M. Lansdorp and Nan-ping Weng

in Human Molecular Genetics

Volume 12, issue 11, pages 1329-1336
Published in print June 2003 | ISSN: 0964-6906
Published online June 2003 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddg139
Telomere length and the expression of natural telomeric genes in human fibroblasts

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Progressive telomere shortening occurs with division of normal human cells, and eventually leads to replicative senescence. The mechanism by which the shortened telomeres cause growth arrest is largely unknown. Transcriptional silencing of genes adjacent to telomeres, also called telomere position effect, has been hypothesized as a possible mechanism of telomere-mediated senescence. However, there is no report regarding telomere position effect on natural telomeric genes in human cells. To address whether the expression of natural telomeric genes is regulated by telomere length, we combined quantitative RT–PCR with quantitative fluorescence in situ hybridization to comparatively analyze the expression of 34 telomeric genes and telomere length of their 24 corresponding chromosome ends in young and senescent human fibroblasts. We have demonstrated here that telomere length alone is not sufficient to determine the expression status of natural telomeric genes. An extended analysis of a tandem of eight telomeric genes on a single chromosome end revealed a discontinuous pattern of changed expression during telomere shortening and some of the changes are senescence-specific rather than non-dividing-related. These results suggest that the expression of natural telomeric genes may be influenced by alteration of local heterochromatin structure.

Journal Article.  4630 words.  Illustrated.

Subjects: Genetics and Genomics

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