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.
Type de document :
Article dans une revue
PLoS Computational Biology, Public Library of Science, 2012, 8 (4), pp.e1002443. 〈10.1371/journal.pcbi.1002443〉
Liste complète des métadonnées

Littérature citée [61 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00706043
Contributeur : Delphine Autard <>
Soumis le : vendredi 8 juin 2012 - 17:33:04
Dernière modification le : mardi 24 avril 2018 - 17:20:13
Document(s) archivé(s) le : lundi 10 septembre 2012 - 16:55:09

Fichier

journal.pcbi.1002443.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Antoine Baker, Benjamin Audit, Chun-Long Chen, Benoit Moindrot, Antoine Leleu, et al.. Replication fork polarity gradients revealed by megabase-sized U-shaped replication timing domains in human cell lines.. PLoS Computational Biology, Public Library of Science, 2012, 8 (4), pp.e1002443. 〈10.1371/journal.pcbi.1002443〉. 〈inserm-00706043〉

Partager

Métriques

Consultations de la notice

812

Téléchargements de fichiers

215