Replication fork polarity gradients revealed by megabase-sized U-shaped replication timing domains in human cell lines.

Antoine Baker 1, 2 Benjamin Audit 1, 2 Chun-Long Chen 3 Benoit Moindrot 1 Antoine Leleu 1 Guillaume Guilbaud 4 Aurélien Rappailles 4 Cédric Vaillant 1, 2 Arach Goldar 5 Fabien Mongelard 1, 6 Yves D'Aubenton-Carafa 3 Olivier Hyrien 4 Claude Thermes 3 Alain Arneodo 1, 2, *
* Auteur correspondant
1 Laboratoire Joliot Curie
2 Phys-ENS - Laboratoire de Physique de l'ENS Lyon
3 CGM - Centre de génétique moléculaire
4 IBENS - Institut de biologie de l'ENS Paris (UMR 8197/1024)
5 IBITECS - Institut de Biologie et de Technologies de Saclay
6 LBMC - Laboratoire de Biologie Moléculaire de la Cellule
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.
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PLoS Computational Biology, Public Library of Science, 2012, 8 (4), pp.e1002443. 〈10.1371/journal.pcbi.1002443〉
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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〉

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