Genome-wide studies highlight indirect links between human replication origins and gene regulation.
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.
Cadoret
Jean-Charles
JC
Institut Jacques Monod, Centre National de la Recherche Scientifique, University Paris 7, 75251 Paris Cedex 5, France.
Meisch
Françoise
F
Hassan-Zadeh
Vahideh
V
Luyten
Isabelle
I
Guillet
Claire
C
Duret
Laurent
L
Quesneville
Hadi
H
Prioleau
Marie-Noëlle
MN
D002843:Chromatin; D018899:CpG Islands; D005786:Gene Expression Regulation; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D050436:Regulatory Elements, Transcriptional; D018741:Replication Origin / Q000235:genetics*
D002843:Chromatin; D016760:Proto-Oncogene Proteins c-fos; D048031:JNK Mitogen-Activated Protein Kinases