title: Telomere position effect in human cells.
abstract: 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.
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9039, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Baur
authors.forename: Y
authors.initials: Y
authors.lastname: Zou
authors.forename: J W
authors.initials: JW
authors.lastname: Shay
authors.forename: W E
authors.initials: WE
authors.lastname: Wright
mesh_terms: 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
chemical_list: D004268:DNA-Binding Proteins; D006877:Hydroxamic Acids; C422952:telomerase RNA; C012589:trichostatin A; D012313:RNA; D008156:Luciferases; D019098:Telomerase