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

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 RNA copy/cell), firing throughout the entire S and mapping to TSSs of ncRNAs. These findings are compatible with a scenario whereby TSS expression levels influence the efficiency of ORC1 recruitment at G(1) and the probability of firing during S.

journal_name

Genome Res

journal_title

Genome research

authors

Dellino GI,Cittaro D,Piccioni R,Luzi L,Banfi S,Segalla S,Cesaroni M,Mendoza-Maldonado R,Giacca M,Pelicci PG

doi

10.1101/gr.142331.112

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

1-11

issue

1

eissn

1088-9051

issn

1549-5469

pii

gr.142331.112

journal_volume

23

pub_type

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