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PMID: 17568004 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Pan-S replication patterns and chromosomal domains defined by genome-tiling arrays of ENCODE genomic areas.

Genome research ·Vol. 17 ·No. 6 ·2007-06-00 ·Pages 865-76

Karnani N, Taylor C, Malhotra A, Dutta A

Abstract

In eukaryotes, accurate control of replication time is required for the efficient completion of S phase and maintenance of genome stability. We present a high-resolution genome-tiling array-based profile of replication timing for approximately 1% of the human genome studied by The ENCODE Project Consortium. Twenty percent of the investigated segments replicate asynchronously (pan-S). These areas are rich in genes and CpG islands, features they share with early-replicating loci. Interphase FISH showed that pan-S replication is a consequence of interallelic variation in replication time and is not an artifact derived from a specific cell cycle synchronization method or from aneuploidy. The interallelic variation in replication time is likely due to interallelic variation in chromatin environment, because while the early- or late-replicating areas were exclusively enriched in activating or repressing histone modifications, respectively, the pan-S areas had both types of histone modification. The replication profile of the chromosomes identified contiguous chromosomal segments of hundreds of kilobases separated by smaller segments where the replication time underwent an acute transition. Close examination of one such segment demonstrated that the delay of replication time was accompanied by a decrease in level of gene expression and appearance of repressive chromatin marks, suggesting that the transition segments are boundary elements separating chromosomal domains with different chromatin environments.

MeSH Terms
Chromatin/metabolism Chromosomes, Human/metabolism DNA Replication/physiology Gene Expression Profiling Genome, Human/physiology Genomic Instability/physiology HeLa Cells Histones/metabolism Humans Oligonucleotide Array Sequence Analysis Protein Processing, Post-Translational/physiology Quantitative Trait Loci/physiology S Phase/physiology
Chemicals
Chromatin Histones
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Karnani Neerja
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22908, USA.
Taylor Christopher
Malhotra Ankit
Dutta Anindya
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Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
DOI
10.1101/gr.5427007
Published
2007-06-00
Pages
865-76
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC1891345
Subset
IM
Grants
NHGRI NIH HHS · U01 HG003157-03 · United States
NCI NIH HHS · R01 CA060499 · United States
NHGRI NIH HHS · HG003157 · United States
NHGRI NIH HHS · U01 HG003157 · United States
NHGRI NIH HHS · U01 HG003157-02 · United States
NCI NIH HHS · R01 CA060499-14 · United States
External Links
PubMed source DOI: 10.1101/gr.5427007 PMC Full Text View journal details
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