Telomere position effect in human cells.
In yeast, telomere position effect (TPE) results in the reversible silencing of genes near telomeres. Here we demonstrate the presence of TPE in human cells. HeLa clones containing a luciferase reporter adjacent to a newly formed telomere express 10 times less luciferase than do control clones generated by random integration. Luciferase expression is restored by trichostatin A, a histone deacetylase inhibitor. Overexpression of a human telomerase reverse transcriptase complementary DNA results in telomere elongation and an additional 2- to 10-fold decrease in expression in telomeric clones but not control clones. The dependence of TPE on telomere length provides a mechanism for the modification of gene expression throughout the replicative life-span of human cells.
Baur
J A
JA
Department of Cell Biology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9039, USA.
Zou
Y
Y
Shay
J W
JW
Wright
W E
WE
D002455:Cell Division; D016922:Cellular Senescence; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D020868:Gene Silencing; D017930:Genes, Reporter; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D012313:RNA; D012190:Retroviridae / Q000235:genetics; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D019076:Transgenes
D004268:DNA-Binding Proteins; D006877:Hydroxamic Acids; C422952:telomerase RNA; C012589:trichostatin A; D012313:RNA; D008156:Luciferases; D019098:Telomerase