Transcription initiation activity sets replication origin efficiency in mammalian cells

  • Sequeira-Mendes J
  • Díaz-Uriarte R
  • Apedaile A
 et al. 
  • 99

    Readers

    Mendeley users who have this article in their library.
  • 137

    Citations

    Citations of this article.

Abstract

Genomic mapping of DNA replication origins (ORIs) in mammals provides a powerful means for understanding the regulatory complexity of our genome. Here we combine a genome-wide approach to identify preferential sites of DNA replication initiation at 0.4% of the mouse genome with detailed molecular analysis at distinct classes of ORIs according to their location relative to the genes. Our study reveals that 85% of the replication initiation sites in mouse embryonic stem (ES) cells are associated with transcriptional units. Nearly half of the identified ORIs map at promoter regions and, interestingly, ORI density strongly correlates with promoter density, reflecting the coordinated organisation of replication and transcription in the mouse genome. Detailed analysis of ORI activity showed that CpG island promoter-ORIs are the most efficient ORIs in ES cells and both ORI specification and firing efficiency are maintained across cell types. Remarkably, the distribution of replication initiation sites at promoter-ORIs exactly parallels that of transcription start sites (TSS), suggesting a co-evolution of the regulatory regions driving replication and transcription. Moreover, we found that promoter-ORIs are significantly enriched in CAGE tags derived from early embryos relative to all promoters. This association implies that transcription initiation early in development sets the probability of ORI activation, unveiling a new hallmark in ORI efficiency regulation in mammalian cells.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text

Authors

  • Joana Sequeira-Mendes

  • Ramón Díaz-Uriarte

  • Anwyn Apedaile

  • Derek Huntley

  • Neil Brockdorff

  • María Gómez

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free