Relating mammalian replication program to large-scale chromatin folding

  • Authors:

  • B. Audit;A. Baker;R. E. Boulos;H. Julienne;A. Arneodo;C. L. Chen;Y. d'Aubenton-Carafa;C. Thermes;A. Goldar;G. Guilbaud;A. Rappailles;O. Hyrien

  • Affiliations:

  • Laboratoire de Physique, ENS-Lyon, CNRS UMR 5672, Lyon, France;Laboratoire de Physique, ENS-Lyon, CNRS UMR 5672, Lyon, France;Laboratoire de Physique, ENS-Lyon, CNRS UMR 5672, Lyon, France;Laboratoire de Physique, ENS-Lyon, CNRS UMR 5672, Lyon, France;Laboratoire de Physique, ENS-Lyon, CNRS UMR 5672, Lyon, France;Centre de Génétique Moléculaire, CNRS UPR 3404, Gif-sur-Yvette, France;Centre de Génétique Moléculaire, CNRS UPR 3404, Gif-sur-Yvette, France;Centre de Génétique Moléculaire, CNRS UPR 3404, Gif-sur-Yvette, France;Commissariat à l'Energie Atomique (CEA), iBiTec-S, Gif-sur-Yvette, France;Institut de Biologie de l'ENS (IBENS), CNRS UMR8197, INSERM U1024, Paris, France;Institut de Biologie de l'ENS (IBENS), CNRS UMR8197, INSERM U1024, Paris, France;Institut de Biologie de l'ENS (IBENS), CNRS UMR8197, INSERM U1024, Paris, France

  • Venue:
  • Proceedings of the International Conference on Bioinformatics, Computational Biology and Biomedical Informatics
  • Year:
  • 2013

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Abstract

We review the existence of a new type of megabase-sized replication domains along the human genome. These domains are revealed in 7 somatic cell types by U-shaped patterns in the replication timing profiles. In the germline, these domains appear as N-shaped patterns in the DNA compositional asymmetry profiles resulting from replication-associated mutational asymmetries. We demonstrated that the average replication fork polarity is directly proportional to both the DNA compositional asymmetry and the derivative of the replication timing profile. Hence, the average fork polarity changes in a linear manner across U/N-replication domains enlightening a robust mode of replication across cell types and during evolution. Using genome-wide chromatin conformation data, we found that the replication domains remarkably coincide with self-interacting folding units of the chromatin fiber and that their borders are long-range interconnected hubs in the chromatin interaction graph. Altogether our results suggest that the spatio-temporal replication program is intimately coupled to a high-order 3D organization of the human genome.