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

Research output: Contribution to journalArticle

Authors

  • Bahar Kasaai
  • Pau Biak Sang
  • Isabelle Peiffer
  • Marie Artufel
  • Gabrielle Smith
  • Marta Rodriguez-Martinez
  • Manuela Romano
  • Sandrina Kinet
  • Charles Theillet
  • Naomi Taylor
  • Benoit Ballester
  • Marcel Méchali

Colleges, School and Institutes

Abstract

DNA replication initiates from multiple genomic locations called replication origins. In metazoa, DNA sequence elements involved in origin specification remain elusive. We examined 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.

Details

Original languageEnglish
Article number4826
Number of pages15
JournalNature Communications
Volume11
Publication statusPublished - 21 Sep 2020

Keywords

  • DNA replication origins, DNA replication initiation, TAD domains, cancer, p53