Genome-wide mapping of human DNA-replication origins: Levels of transcription at ORC1 sites regulate origin selection and replication timing

Gaetano Ivan Dellino, Davide Cittaro, Rossana Piccioni, Lucilla Luzi, Stefania Banfi, Simona Segalla, Matteo Cesaroni, Ramiro Mendoza-Maldonado, Mauro Giacca, Pier Giuseppe Pelicci

Research output: Contribution to journalArticlepeer-review

Abstract

We report the genome-wide mapping of ORC1 binding sites in mammals, by chromatin immunoprecipitation and parallel sequencing (ChIP-seq). ORC1 binding sites in HeLa cells were validated as active DNA replication origins (ORIs) using Repli-seq, a method that allows identification of ORI-containing regions by parallel sequencing of temporally ordered replicating DNA. ORC1 sites were universally associated with transcription start sites (TSSs) of coding or noncoding RNAs (ncRNAs). Transcription levels at the ORC1 sites directly correlated with replication timing, suggesting the existence of two classes of ORIs: those associated with moderate/high transcription levels (≥1 RNA copy/cell), firing in early S and mapping to the TSSs of coding RNAs; and those associated with low transcription levels (1 and the probability of firing during S.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalGenome Research
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 2013

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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