title: Replication landscape of the human genome.
abstract: Despite intense investigation, human replication origins and termini remain elusive. Existing data have shown strong discrepancies. Here we sequenced highly purified Okazaki fragments from two cell types and, for the first time, quantitated replication fork directionality and delineated initiation and termination zones genome-wide. Replication initiates stochastically, primarily within non-transcribed, broad (up to 150 kb) zones that often abut transcribed genes, and terminates dispersively between them. Replication fork progression is significantly co-oriented with the transcription. Initiation and termination zones are frequently contiguous, sometimes separated by regions of unidirectional replication. Initiation zones are enriched in open chromatin and enhancer marks, even when not flanked by genes, and often border 'topologically associating domains' (TADs). Initiation zones are enriched in origin recognition complex (ORC)-binding sites and better align to origins previously mapped using bubble-trap than λ-exonuclease. This novel panorama of replication reveals how chromatin and transcription modulate the initiation process to create cell-type-specific replication programs.
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, 46 rue d'Ulm, Paris F-75005, France.|Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, UMR 9198, FRC 3115, Avenue de la Terrasse, Bâtiment 24, Gif-sur-Yvette, Paris F-91198, France.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Petryk
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, 46 rue d'Ulm, Paris F-75005, France.
authors.forename: Malik
authors.initials: M
authors.lastname: Kahli
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, UMR 9198, FRC 3115, Avenue de la Terrasse, Bâtiment 24, Gif-sur-Yvette, Paris F-91198, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: d'Aubenton-Carafa
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, UMR 9198, FRC 3115, Avenue de la Terrasse, Bâtiment 24, Gif-sur-Yvette, Paris F-91198, France.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jaszczyszyn
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, UMR 9198, FRC 3115, Avenue de la Terrasse, Bâtiment 24, Gif-sur-Yvette, Paris F-91198, France.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, UMR 9198, FRC 3115, Avenue de la Terrasse, Bâtiment 24, Gif-sur-Yvette, Paris F-91198, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Silvain
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, UMR 9198, FRC 3115, Avenue de la Terrasse, Bâtiment 24, Gif-sur-Yvette, Paris F-91198, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Thermes
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, UMR 9198, FRC 3115, Avenue de la Terrasse, Bâtiment 24, Gif-sur-Yvette, Paris F-91198, France.
authors.forename: Chun-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), and Inserm U1024, and CNRS UMR 8197, 46 rue d'Ulm, Paris F-75005, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hyrien
mesh_terms: D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism; D004247:DNA; D004261:DNA Replication; D015894:Genome, Human; D006657:Histones / Q000378:metabolism; D006801:Humans; D051738:Origin Recognition Complex / Q000378:metabolism*; D018741:Replication Origin; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones; C022262:Okazaki fragments; D051738:Origin Recognition Complex; D004247:DNA