RT Journal
A1 Dellino, Gaetano Ivan
A1 Cittaro, Davide
A1 Piccioni, Rossana
A1 Luzi, Lucilla
A1 Banfi, Stefania
A1 Segalla, Simona
A1 Cesaroni, Matteo
A1 Mendoza-Maldonado, Ramiro
A1 Giacca, Mauro
A1 Pelicci, Pier Giuseppe
T1 Genome-wide mapping of human DNA-replication origins: Levels of transcription at ORC1 sites regulate origin selection and replication timing
JF Genome Research 
JO Genome Research 
YR 2013 
FD January 01 
VO 23 
IS 1 
SP 1 
OP 11 
DO 10.1101/gr.142331.112 
UL http://genome.cshlp.org/content/23/1/1.abstract 
AB 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 G1 and the probability of firing during S.