title: The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats.
abstract: The study of the proteins that bind to telomeric DNA in mammals has provided a deep understanding of the mechanisms involved in chromosome-end protection. However, very little is known on the binding of these proteins to nontelomeric DNA sequences. The TTAGGG DNA repeat proteins 1 and 2 (TRF1 and TRF2) bind to mammalian telomeres as part of the shelterin complex and are essential for maintaining chromosome end stability. In this study, we combined chromatin immunoprecipitation with high-throughput sequencing to map at high sensitivity and resolution the human chromosomal sites to which TRF1 and TRF2 bind. While most of the identified sequences correspond to telomeric regions, we showed that these two proteins also bind to extratelomeric sites. The vast majority of these extratelomeric sites contains interstitial telomeric sequences (or ITSs). However, we also identified non-ITS sites, which correspond to centromeric and pericentromeric satellite DNA. Interestingly, the TRF-binding sites are often located in the proximity of genes or within introns. We propose that TRF1 and TRF2 couple the functional state of telomeres to the long-range organization of chromosomes and gene regulation networks by binding to extratelomeric sequences.
authors.affiliation: Laboratoire de Biologie Moléculaire de la Cellule-UMR 5239 CNRS/ENS Lyon/ Université Lyon, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, Lyon 69364, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Simonet
authors.forename: Laure-Emmanuelle
authors.initials: LE
authors.lastname: Zaragosi
authors.forename: Claude
authors.initials: C
authors.lastname: Philippe
authors.forename: Kevin
authors.initials: K
authors.lastname: Lebrigand
authors.forename: Clémentine
authors.initials: C
authors.lastname: Schouteden
authors.forename: Adeline
authors.initials: A
authors.lastname: Augereau
authors.forename: Serge
authors.initials: S
authors.lastname: Bauwens
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.forename: Marco
authors.initials: M
authors.lastname: Santagostino
authors.forename: Elena
authors.initials: E
authors.lastname: Giulotto
authors.forename: Frederique
authors.initials: F
authors.lastname: Magdinier
authors.forename: Béatrice
authors.initials: B
authors.lastname: Horard
authors.forename: Pascal
authors.initials: P
authors.lastname: Barbry
authors.forename: Rainer
authors.initials: R
authors.lastname: Waldmann
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D005796:Genes; D006801:Humans; D011485:Protein Binding; D016615:Telomere; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism*
chemical_list: D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D004247:DNA