title: Subtelomeric CTCF and cohesin binding site organization using improved subtelomere assemblies and a novel annotation pipeline.
abstract: Mapping genome-wide data to human subtelomeres has been problematic due to the incomplete assembly and challenges of low-copy repetitive DNA elements. Here, we provide updated human subtelomere sequence assemblies that were extended by filling telomere-adjacent gaps using clone-based resources. A bioinformatic pipeline incorporating multiread mapping for annotation of the updated assemblies using short-read data sets was developed and implemented. Annotation of subtelomeric sequence features as well as mapping of CTCF and cohesin binding sites using ChIP-seq data sets from multiple human cell types confirmed that CTCF and cohesin bind within 3 kb of the start of terminal repeat tracts at many, but not all, subtelomeres. CTCF and cohesin co-occupancy were also enriched near internal telomere-like sequence (ITS) islands and the nonterminal boundaries of subtelomere repeat elements (SREs) in transformed lymphoblastoid cell lines (LCLs) and human embryonic stem cell (ES) lines, but were not significantly enriched in the primary fibroblast IMR90 cell line. Subtelomeric CTCF and cohesin sites predicted by ChIP-seq using our bioinformatics pipeline (but not predicted when only uniquely mapping reads were considered) were consistently validated by ChIP-qPCR. The colocalized CTCF and cohesin sites in SRE regions are candidates for mediating long-range chromatin interactions in the transcript-rich SRE region. A public browser for the integrated display of short-read sequence-based annotations relative to key subtelomere features such as the start of each terminal repeat tract, SRE identity and organization, and subtelomeric gene models was established.
authors.affiliation: Graduate Group in Genomics and Computational Biology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; The Wistar Institute, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Nicholas
authors.initials: N
authors.lastname: Stong
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Zhong
authors.initials: Z
authors.lastname: Deng
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Ravi
authors.initials: R
authors.lastname: Gupta
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Sufen
authors.initials: S
authors.lastname: Hu
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Shiela
authors.initials: S
authors.lastname: Paul
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Amber K
authors.initials: AK
authors.lastname: Weiner
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.affiliation: The Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Graves
authors.affiliation: The Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
authors.forename: Catrina C
authors.initials: CC
authors.lastname: Fronick
authors.affiliation: The Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Courtney
authors.affiliation: The Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Paul M
authors.initials: PM
authors.lastname: Lieberman
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Ramana V
authors.initials: RV
authors.lastname: Davuluri
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Harold
authors.initials: H
authors.lastname: Riethman
mesh_terms: D001483:Base Sequence; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000235:genetics*; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015894:Genome, Human; D006801:Humans; D058977:Molecular Sequence Annotation / Q000379:methods; D008969:Molecular Sequence Data; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000235:genetics*; D020079:Terminal Repeat Sequences; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D012097:Repressor Proteins; D000097722:Cohesins; C000619697:CTCF protein, human