A predictable conserved DNA base composition signature defines human core DNA replication origins

Ildem Akerman (), Bahar Kasaai, Alina Bazarova, Pau Biak Sang, Isabelle Peiffer, Marie Artufel, Romain Derelle, Gabrielle Smith, Marta Rodriguez-Martinez, Manuela Romano, Sandrina Kinet, Peter Tino, Charles Theillet, Naomi Taylor, Benoit Ballester and Marcel Méchali ()
Additional contact information
Ildem Akerman: CNRS - University of Montpellier
Bahar Kasaai: CNRS - University of Montpellier
Alina Bazarova: University of Birmingham
Pau Biak Sang: CNRS - University of Montpellier
Isabelle Peiffer: CNRS - University of Montpellier
Marie Artufel: Aix-Marseille University, INSERM, TAGC, UMR S1090
Romain Derelle: University of Birmingham
Gabrielle Smith: University of Birmingham
Marta Rodriguez-Martinez: CNRS - University of Montpellier
Manuela Romano: University of Montpellier, CNRS
Sandrina Kinet: University of Montpellier, CNRS
Peter Tino: University of Birmingham
Charles Theillet: Institut de Recherche en Cancérologie de Montpellier (IRCM)
Naomi Taylor: University of Montpellier, CNRS
Benoit Ballester: Aix-Marseille University, INSERM, TAGC, UMR S1090
Marcel Méchali: CNRS - University of Montpellier

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract DNA replication initiates from multiple genomic locations called replication origins. In metazoa, DNA sequence elements involved in origin specification remain elusive. Here, we examine pluripotent, primary, differentiating, and immortalized human cells, and demonstrate that a class of origins, termed core origins, is shared by different cell types and host ~80% of all DNA replication initiation events in any cell population. We detect a shared G-rich DNA sequence signature that coincides with most core origins in both human and mouse genomes. Transcription and G-rich elements can independently associate with replication origin activity. Computational algorithms show that core origins can be predicted, based solely on DNA sequence patterns but not on consensus motifs. Our results demonstrate that, despite an attributed stochasticity, core origins are chosen from a limited pool of genomic regions. Immortalization through oncogenic gene expression, but not normal cellular differentiation, results in increased stochastic firing from heterochromatin and decreased origin density at TAD borders.

Date: 2020
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DOI: 10.1038/s41467-020-18527-0

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