title: Replication fork polarity gradients revealed by megabase-sized U-shaped replication timing domains in human cell lines.
abstract: In higher eukaryotes, replication program specification in different cell types remains to be fully understood. We show for seven human cell lines that about half of the genome is divided in domains that display a characteristic U-shaped replication timing profile with early initiation zones at borders and late replication at centers. Significant overlap is observed between U-domains of different cell lines and also with germline replication domains exhibiting a N-shaped nucleotide compositional skew. From the demonstration that the average fork polarity is directly reflected by both the compositional skew and the derivative of the replication timing profile, we argue that the fact that this derivative displays a N-shape in U-domains sustains the existence of large-scale gradients of replication fork polarity in somatic and germline cells. Analysis of chromatin interaction (Hi-C) and chromatin marker data reveals that U-domains correspond to high-order chromatin structural units. We discuss possible models for replication origin activation within U/N-domains. The compartmentalization of the genome into replication U/N-domains provides new insights on the organization of the replication program in the human genome.
authors.affiliation: Université de Lyon, Lyon, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Baker
authors.forename: Benjamin
authors.initials: B
authors.lastname: Audit
authors.forename: Chun-Long
authors.initials: CL
authors.lastname: Chen
authors.forename: Benoit
authors.initials: B
authors.lastname: Moindrot
authors.forename: Antoine
authors.initials: A
authors.lastname: Leleu
authors.forename: Guillaume
authors.initials: G
authors.lastname: Guilbaud
authors.forename: Aurélien
authors.initials: A
authors.lastname: Rappailles
authors.forename: Cédric
authors.initials: C
authors.lastname: Vaillant
authors.forename: Arach
authors.initials: A
authors.lastname: Goldar
authors.forename: Fabien
authors.initials: F
authors.lastname: Mongelard
authors.forename: Yves
authors.initials: Y
authors.lastname: d'Aubenton-Carafa
authors.forename: Olivier
authors.initials: O
authors.lastname: Hyrien
authors.forename: Claude
authors.initials: C
authors.lastname: Thermes
authors.forename: Alain
authors.initials: A
authors.lastname: Arneodo
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping / Q000379:methods*; D003198:Computer Simulation; D004247:DNA / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D016678:Genome / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D018741:Replication Origin / Q000235:genetics*
chemical_list: D004247:DNA