Telomere length and the expression of natural telomeric genes in human fibroblasts
Telomere length and the expression of natural telomeric genes in human fibroblasts
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DOI：
10.1093/hmg/ddg139
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发表时间：
2003-06-01
影响因子：
3.5
通讯作者：
Weng, NP
中科院分区：
文献类型：
--
作者：
Ning, Y;Xu, JF;Weng, NP
随着正常人类细胞的分裂，端粒逐渐缩短，并最终导致复制性衰老。缩短的端粒导致生长停滞的机制在很大程度上是未知的。端粒附近基因的转录沉默，也称为端粒位置效应，已被假设为端粒介导的衰老的可能机制。然而，目前还没有关于端粒位置对人类细胞中天然端粒基因影响的报道。为了研究天然端粒基因的表达是否受端粒长度的调控，我们将定量RT-PCR与定量荧光原位杂交相结合，对比分析了34个端粒基因在年轻和衰老人成纤维细胞中的表达及其对应的24条染色体末端的端粒长度。我们已经证明，端粒长度本身并不足以决定天然端粒基因的表达状态。对单个染色体末端的8个端粒基因串联的扩展分析揭示了端粒缩短过程中表达变化的不连续模式，其中一些变化是衰老特异性的，而不是与分裂相关的。这些结果表明，天然端粒基因的表达可能受到局部异染色质结构改变的影响。
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.