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Megabase Replication Domains Along the Human Genome: Relation to Chromatin Structure and Genome Organisation

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Epigenetics: Development and Disease

Part of the book series: Subcellular Biochemistry ((SCBI,volume 61))

Abstract

In higher eukaryotes, the absence of specific sequence motifs, marking the origins of replication has been a serious hindrance to the understanding of (i) the mechanisms that regulate the spatio-temporal replication program, and (ii) the links between origins activation, chromatin structure and transcription. In this chapter, we review the partitioning of the human genome into megabased-size replication domains delineated as N-shaped motifs in the strand compositional asymmetry profiles. They collectively span 28.3% of the genome and are bordered by more than 1,000 putative replication origins. We recapitulate the comparison of this partition of the human genome with high-resolution experimental data that confirms that replication domain borders are likely to be preferential replication initiation zones in the germline. In addition, we highlight the specific distribution of experimental and numerical chromatin marks along replication domains. Domain borders correspond to particular open chromatin regions, possibly encoded in the DNA sequence, and around which replication and transcription are highly coordinated. These regions also present a high evolutionary breakpoint density, suggesting that susceptibility to breakage might be linked to local open chromatin fiber state. Altogether, this chapter presents a compartmentalization of the human genome into replication domains that are landmarks of the human genome organization and are likely to play a key role in genome dynamics during evolution and in pathological situations.

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Acknowledgements

We thank G. Chevereau, G. Guilbaud, O. Hyrien, H. Julienne, O. Rappailles and C. Vaillant for helpful discussions. This work was supported by ACI IMPBio2004, the PAI Tournesol and the Agence Nationale de la Recherche under project HUGOREP (ANR PCV 2005) and REFOPOL (ANR BLANC SVSE6).

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Authors and Affiliations

  1. Université de Lyon, F-69000, Lyon, France

    Benjamin Audit, Lamia Zaghloul, Antoine Baker & Alain Arneodo

  2. Laboratoire de Physique, CNRS, Ecole Normale Supérieure de Lyon, F-69007, Lyon, France

    Benjamin Audit, Lamia Zaghloul, Antoine Baker & Alain Arneodo

  3. Centre de Génétique Moléculaire, CNRS, F-91198, Gif-sur-Yvette, France

    Chun-Long Chen, Yves d’Aubenton-Carafa & Claude Thermes

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  1. Benjamin Audit
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  2. Lamia Zaghloul
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Correspondence to Benjamin Audit .

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  1. Advanced Scientific Research, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for, Jakkur P.O., Bangalore, 560064, India

    Tapas K. Kundu

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Audit, B. et al. (2013). Megabase Replication Domains Along the Human Genome: Relation to Chromatin Structure and Genome Organisation. In: Kundu, T. (eds) Epigenetics: Development and Disease. Subcellular Biochemistry, vol 61. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4525-4_3

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