title: Human telomeric proteins occupy selective interstitial sites.
abstract: Human telomeres are bound and protected by protein complexes assembled around the six core telomeric proteins RAP1, TRF1, TRF2, TIN2, TPP1, and POT1. The function of these proteins on telomeres has been studied extensively. Recently, increasing evidence has suggested possible roles for these proteins outside of telomeres. However, the non-canonical (extra-telomeric) function of human telomeric proteins remains poorly understood. To this end, we systematically investigated the binding sites of telomeric proteins along human chromosomes, by performing whole-genome chromatin immunoprecipitation (ChIP) for RAP1 and TRF2. ChIP sequencing (ChIP-seq) revealed that RAP1 and TRF2 could be found on a small number of interstitial sites, including regions that are proximal to genes. Some of these binding sites contain short telomere repeats, suggesting that telomeric proteins could directly bind to interstitial sites. Interestingly, only a small fraction of the available interstitial telomere repeat-containing regions were occupied by RAP1 and TRF2. Ectopically expressed TRF2 was able to occupy additional interstitial telomere repeat sites, suggesting that protein concentration may dictate the selective targeting of telomeric proteins to interstitial sites. Reducing RAP1 and TRF2 expression by RNA interference led to altered transcription of RAP1- and TRF2-targeted genes. Our results indicate that human telomeric proteins could occupy a limited number of interstitial sites and regulate gene transcription.
authors.affiliation: Verna and Marrs Mclean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.forename: Yuanyan
authors.initials: Y
authors.lastname: Xiong
authors.forename: Hyeung
authors.initials: H
authors.lastname: Kim
authors.forename: Quanyuan
authors.initials: Q
authors.lastname: He
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Zhou
authors.initials: Z
authors.lastname: Songyang
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D015894:Genome, Human; D006801:Humans; D011485:Protein Binding; D000089804:Shelterin Complex; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: C495876:ACD protein, human; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2