Format

Send to

Choose Destination
PLoS Comput Biol. 2012;8(4):e1002443. doi: 10.1371/journal.pcbi.1002443. Epub 2012 Apr 5.

Replication fork polarity gradients revealed by megabase-sized U-shaped replication timing domains in human cell lines.

Author information

1
Université de Lyon, Lyon, France.

Abstract

In higher eukaryotes, replication program specification in different cell types remains to be fully understood. We show for seven human cell lines that about half of the genome is divided in domains that display a characteristic U-shaped replication timing profile with early initiation zones at borders and late replication at centers. Significant overlap is observed between U-domains of different cell lines and also with germline replication domains exhibiting a N-shaped nucleotide compositional skew. From the demonstration that the average fork polarity is directly reflected by both the compositional skew and the derivative of the replication timing profile, we argue that the fact that this derivative displays a N-shape in U-domains sustains the existence of large-scale gradients of replication fork polarity in somatic and germline cells. Analysis of chromatin interaction (Hi-C) and chromatin marker data reveals that U-domains correspond to high-order chromatin structural units. We discuss possible models for replication origin activation within U/N-domains. The compartmentalization of the genome into replication U/N-domains provides new insights on the organization of the replication program in the human genome.

PMID:
22496629
PMCID:
PMC3320577
DOI:
10.1371/journal.pcbi.1002443
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center