Human telomeric proteins occupy selective interstitial sites

• Published in: Cell research Vol. 21; no. 7; pp. 1013 - 1027
• Main Authors: Yang, Dong, Xiong, Yuanyan, Kim, Hyeung, He, Quanyuan, Li, Yumei, Chen, Rui, Songyang, Zhou
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2011; Nature Publishing Group
• Subjects: 631/208/200; 631/45/612/1229; 631/80/103/560; Base Sequence; Binding Sites; Biomedical and Life Sciences; Cell Biology; Cell Line; Chromatin; Chromatin Immunoprecipitation; Chromosomes; Genome, Human; Humans; Immunoprecipitation; Life Sciences; Original; original-article; Protein Binding; Proteins; RAP1; Rap1 protein; RNA-mediated interference; Telomere - metabolism; Telomere-binding protein; Telomere-Binding Proteins - metabolism; Telomeres; Telomeric Repeat Binding Protein 2 - metabolism; Transcription; Transcriptional Activation; TRF2 protein; 人类; 位置; 染色体端粒; 染色质免疫沉淀; 结合位点; 蛋白复合物; 间隙; ChIP-sequencing; ChIP; extra-telomeric; TRF2; RAP1; telomere
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2011.39

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.