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作 者:Thomas Simonet Laure-Emmanuelle Zaragosi Claude Philippe Kevin Lebrigand Cldmentine Schouteden Adeline Augereau Serge Bauwens Jing Ye Marco Santagostino Elena Giulotto Frederique Magdinier Beatrice Horard Pascal Barbry Rainer Waldmann Eric Gilson
机构地区:[1]Laboratoire de Biologie Moleculaire de la Cellule-UMR 5239 CNRS/ENS Lyon/Universite Lyon, Ecole Normale Superieure de Lyon, 46 allde d'Italie, Lyon 69364, France [2]CNRS and University of Nice Sophia Antipolis, Institut de Pharmacologie Moleculaire et Cellulaire, 06560 Sophia Antipolis, France [3]Laboratory of Biology and Pathology of Genomes of University of Nice Sophia-Antipolis, CNRS UMR6267/INSERM U998, Faculty of Medicine, Nice, France [4]Dipartimento di Genetica e Microbiologia A driano Buzzati-Traverso, Universita di Pavia, Pavia, Italy [5]Department of Medical Genetics, CHU of Nice, Nice, France
出 处:《Cell Research》2011年第7期1028-1038,共11页细胞研究(英文版)
摘 要: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 te- lomeres 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.
关 键 词:telomere: TRF1 TRF2: interstitial telomeric sequence satellite DNA
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