title: The N-terminal domains of TRF1 and TRF2 regulate their ability to condense telomeric DNA.
abstract: TRF1 and TRF2 are key proteins in human telomeres, which, despite their similarities, have different behaviors upon DNA binding. Previous work has shown that unlike TRF1, TRF2 condenses telomeric, thus creating consequential negative torsion on the adjacent DNA, a property that is thought to lead to the stimulation of single-strand invasion and was proposed to favor telomeric DNA looping. In this report, we show that these activities, originating from the central TRFH domain of TRF2, are also displayed by the TRFH domain of TRF1 but are repressed in the full-length protein by the presence of an acidic domain at the N-terminus. Strikingly, a similar repression is observed on TRF2 through the binding of a TERRA-like RNA molecule to the N-terminus of TRF2. Phylogenetic and biochemical studies suggest that the N-terminal domains of TRF proteins originate from a gradual extension of the coding sequences of a duplicated ancestral gene with a consequential progressive alteration of the biochemical properties of these proteins. Overall, these data suggest that the N-termini of TRF1 and TRF2 have evolved to finely regulate their ability to condense DNA.
authors.affiliation: Université de Lyon, Laboratoire Joliot-Curie, CNRS USR3010, Ecole Normale Supérieure de Lyon, 46, allée d'Italie, F-69364 Lyon, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Poulet
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pisano
authors.forename: Cendrine
authors.initials: C
authors.lastname: Faivre-Moskalenko
authors.forename: Bei
authors.initials: B
authors.lastname: Pei
authors.forename: Yannick
authors.initials: Y
authors.lastname: Tauran
authors.forename: Zofia
authors.initials: Z
authors.lastname: Haftek-Terreau
authors.forename: Frédéric
authors.initials: F
authors.lastname: Brunet
authors.forename: Yann-Vaï
authors.initials: YV
authors.lastname: Le Bihan
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Ledu
authors.forename: Fabien
authors.initials: F
authors.lastname: Montel
authors.forename: Nicolas
authors.initials: N
authors.lastname: Hugo
authors.forename: Simon
authors.initials: S
authors.lastname: Amiard
authors.forename: Françoise
authors.initials: F
authors.lastname: Argoul
authors.forename: Annie
authors.initials: A
authors.lastname: Chaboud
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Giraud-Panis
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism; D035321:Telomeric Repeat Binding Protein 1 / Q000737:chemistry* / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000737:chemistry*
chemical_list: C504753:TERF2 protein, human; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D012313:RNA; D004247:DNA