title: Transcription regulates telomere dynamics in human cancer cells.
abstract: Telomeres are nucleoprotein structures capping the physical ends of linear eukaryotic chromosomes. Although largely heterochromatic, telomeres are transcribed into telomeric repeat-containing RNA (TERRA) molecules by RNA polymerase II. The functions associated with telomere transcription and TERRA remain ill defined. Here we show that the transcriptional activity of human telomeres directly regulates their movement during interphase. We find that chemical inhibition of global transcription dampens telomere motion, while global stimulation promotes it. Likewise, when DNA methyltransferase enzymes are deleted to augment telomere transcription, we observe increased telomere movement. Finally, using a cell line engineered with a unique transcriptionally inducible telomere, we show that transcription of one specific telomere stimulates only its own dynamics without overtly affecting its stability or its length. We reveal a new and unforeseen function for telomere transcription as a regulator of telomere motion, and speculate on the intriguing possibility that transcription-dependent telomere motion sustains the maintenance of functional and dysfunctional telomeres.
authors.affiliation: Institute of Biochemistry, Eidgenössische Technische Hochschule Zürich, CH-8093 Zürich, Switzerland.
authors.forename: Rajika
authors.initials: R
authors.lastname: Arora
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Brun
authors.forename: Claus M
authors.initials: CM
authors.lastname: Azzalin
mesh_terms: D001483:Base Sequence; D002503:Centromere; D015254:DNA Modification Methylases / Q000378:metabolism; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016615:Telomere; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D015254:DNA Modification Methylases