Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 41, Pages 15837-15842Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0805208105
Keywords
chromatin structure; DNA replication origin; ENCODE regions; genome-wide mapping; CpG island
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Funding
- Agence Nationale pour le Recherche [ANR 05-JCJC-0110]
- Association pour la Recherche sur le Cancer
- Ligue contre le Cancer
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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.
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