Unraveling Cell Type-specific and Reprogrammable Human Replication Origin Signatures Associated with G-quadruplex Consensus Motifs

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2012 Jul 4

PMID 22751019

Citations 230

Authors

Emilie Besnard

Amelie Babled

Laure Lapasset

Ollivier Milhavet

Hugues Parrinello

Christelle Dantec

Jean-Michel Marin

Jean-Marc Lemaitre

Affiliations

Soon will be listed here.

Abstract

DNA replication is highly regulated, ensuring faithful inheritance of genetic information through each cell cycle. In metazoans, this process is initiated at many thousands of DNA replication origins whose cell type-specific distribution and usage are poorly understood. We exhaustively mapped the genome-wide location of replication origins in human cells using deep sequencing of short nascent strands and identified ten times more origin positions than we expected; most of these positions were conserved in four different human cell lines. Furthermore, we identified a consensus G-quadruplex-forming DNA motif that can predict the position of DNA replication origins in human cells, accounting for their distribution, usage efficiency and timing. Finally, we discovered a cell type-specific reprogrammable signature of cell identity that was revealed by specific efficiencies of conserved origin positions and not by the selection of cell type-specific subsets of origins.

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References

Dazy S, Gandrillon O, Hyrien O, Prioleau M . Broadening of DNA replication origin usage during metazoan cell differentiation. EMBO Rep. 2006; 7(8):806-11. PMC: 1525144. DOI: 10.1038/sj.embor.7400736. View

DePamphilis M . Eukaryotic DNA replication: anatomy of an origin. Annu Rev Biochem. 1993; 62:29-63. DOI: 10.1146/annurev.bi.62.070193.000333. View

Remus D, Beall E, Botchan M . DNA topology, not DNA sequence, is a critical determinant for Drosophila ORC-DNA binding. EMBO J. 2004; 23(4):897-907. PMC: 380993. DOI: 10.1038/sj.emboj.7600077. View

MacAlpine D, Rodriguez H, Bell S . Coordination of replication and transcription along a Drosophila chromosome. Genes Dev. 2004; 18(24):3094-105. PMC: 535919. DOI: 10.1101/gad.1246404. View

Nicol J, Helt G, Blanchard Jr S, Raja A, Loraine A . The Integrated Genome Browser: free software for distribution and exploration of genome-scale datasets. Bioinformatics. 2009; 25(20):2730-1. PMC: 2759552. DOI: 10.1093/bioinformatics/btp472. View

Dijkwel P, Hamlin J . The Chinese hamster dihydrofolate reductase origin consists of multiple potential nascent-strand start sites. Mol Cell Biol. 1995; 15(6):3023-31. PMC: 230533. DOI: 10.1128/MCB.15.6.3023. View

White E, Emanuelsson O, Scalzo D, Royce T, Kosak S, Oakeley E . DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states. Proc Natl Acad Sci U S A. 2004; 101(51):17771-6. PMC: 539744. DOI: 10.1073/pnas.0408170101. View

Touchon M, Nicolay S, Audit B, Brodie of Brodie E, dAubenton-Carafa Y, Arneodo A . Replication-associated strand asymmetries in mammalian genomes: toward detection of replication origins. Proc Natl Acad Sci U S A. 2005; 102(28):9836-41. PMC: 1174978. DOI: 10.1073/pnas.0500577102. View

Costantini M, Bernardi G . Replication timing, chromosomal bands, and isochores. Proc Natl Acad Sci U S A. 2008; 105(9):3433-7. PMC: 2265141. DOI: 10.1073/pnas.0710587105. View

10.

Conti C, Sacca B, Herrick J, Lalou C, Pommier Y, Bensimon A . Replication fork velocities at adjacent replication origins are coordinately modified during DNA replication in human cells. Mol Biol Cell. 2007; 18(8):3059-67. PMC: 1949372. DOI: 10.1091/mbc.e06-08-0689. View

11.

Norio P, Kosiyatrakul S, Yang Q, Guan Z, Brown N, Thomas S . Progressive activation of DNA replication initiation in large domains of the immunoglobulin heavy chain locus during B cell development. Mol Cell. 2005; 20(4):575-87. DOI: 10.1016/j.molcel.2005.10.029. View

12.

Lemaitre J, Danis E, Pasero P, Vassetzky Y, Mechali M . Mitotic remodeling of the replicon and chromosome structure. Cell. 2005; 123(5):787-801. DOI: 10.1016/j.cell.2005.08.045. View

13.

Aladjem M, Rodewald L, Kolman J, Wahl G . Genetic dissection of a mammalian replicator in the human beta-globin locus. Science. 1998; 281(5379):1005-9. DOI: 10.1126/science.281.5379.1005. View

14.

Halder R, Halder K, Sharma P, Garg G, Sengupta S, Chowdhury S . Guanine quadruplex DNA structure restricts methylation of CpG dinucleotides genome-wide. Mol Biosyst. 2010; 6(12):2439-47. DOI: 10.1039/c0mb00009d. View

15.

Sun D, Hurley L . The importance of negative superhelicity in inducing the formation of G-quadruplex and i-motif structures in the c-Myc promoter: implications for drug targeting and control of gene expression. J Med Chem. 2009; 52(9):2863-74. PMC: 2757002. DOI: 10.1021/jm900055s. View

16.

Hiratani I, Takebayashi S, Lu J, Gilbert D . Replication timing and transcriptional control: beyond cause and effect--part II. Curr Opin Genet Dev. 2009; 19(2):142-9. PMC: 2677117. DOI: 10.1016/j.gde.2009.02.002. View

17.

Blahnik K, Dou L, OGeen H, McPhillips T, Xu X, Cao A . Sole-Search: an integrated analysis program for peak detection and functional annotation using ChIP-seq data. Nucleic Acids Res. 2009; 38(3):e13. PMC: 2817454. DOI: 10.1093/nar/gkp1012. View

18.

Antequera F . Genomic specification and epigenetic regulation of eukaryotic DNA replication origins. EMBO J. 2004; 23(22):4365-70. PMC: 526466. DOI: 10.1038/sj.emboj.7600450. View

19.

Hamlin J, Mesner L, Lar O, Torres R, Chodaparambil S, Wang L . A revisionist replicon model for higher eukaryotic genomes. J Cell Biochem. 2008; 105(2):321-9. PMC: 2574905. DOI: 10.1002/jcb.21828. View

20.

Aladjem M . Replication in context: dynamic regulation of DNA replication patterns in metazoans. Nat Rev Genet. 2007; 8(8):588-600. DOI: 10.1038/nrg2143. View