[en] To get insights into the regulation of replication initiation, we systematically mapped replication origins along 1% of the human genome in HeLa cells. We identified 283 origins, 10 times more than previously known. Origin density is strongly correlated with genomic landscapes, with clusters of closely spaced origins in GC-rich regions and no origins in large GC-poor regions. Origin sequences are evolutionarily conserved, and half of them map within or near CpG islands. Most of the origins overlap transcriptional regulatory elements, providing further evidence of a connection with gene regulation. Moreover, we identify c-JUN and c-FOS as important regulators of origin selection. Half of the identified replication initiation sites do not have an open chromatin configuration, showing the absence of a direct link with gene regulation. Replication timing analyses coupled with our origin mapping suggest that a relatively strict origin-timing program regulates the replication of the human genome.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Cadoret, Jean-Charles; Institut Jacques Monod, Centre National de la Recherche Scientifique, University Paris 7, 75251 Paris Cedex 5, France
MEISCH, Françoise ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Research strategy
Hassan-Zadeh, Vahideh; Institut Jacques Monod, Centre National de la Recherche Scientifique, University Paris 7, 75251 Paris Cedex 5, France ; Université Pierre et Marie Curie, 75005 Paris, France
Luyten, Isabelle; Unité de Recherches en Génomique-Info, Institut National de la Recherche Agronomique, 91000 Évry, France
Guillet, Claire; Centre National de la Recherche Scientifique, Université Lyon 1 ; Unité Mixte de Recherche 5558, Laboratoire de Biométrie et Biologie Evolutive, 69622 Villeurbanne, France
Duret, Laurent; Centre National de la Recherche Scientifique, Université Lyon 1 ; Unité Mixte de Recherche 5558, Laboratoire de Biométrie et Biologie Evolutive, 69622 Villeurbanne, France
Quesneville, Hadi; Université Pierre et Marie Curie, 75005 Paris, France
Prioleau, Marie-Noëlle; Institut Jacques Monod, Centre National de la Recherche Scientifique, University Paris 7, 75251 Paris Cedex 5, France ; Université Pierre et Marie Curie, 75005 Paris, France
External co-authors :
yes
Language :
English
Title :
Genome-wide studies highlight indirect links between human replication origins and gene regulation.
Publication date :
14 October 2008
Journal title :
Proceedings of the National Academy of Sciences of the United States of America
ISSN :
0027-8424
eISSN :
1091-6490
Publisher :
Proceedings of the National Academy of Sciences, United States
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