Comptes Rendus
Gene organization inside replication domains in mammalian genomes
Comptes Rendus. Mécanique, Volume 340 (2012) no. 11-12, pp. 745-757.

We investigate the large-scale organization of human genes with respect to “master” replication origins that were previously identified as bordering nucleotide compositional skew domains. We separate genes in two categories depending on their CpG enrichment at the promoter which can be considered as a marker of germline DNA methylation. Using expression data in mouse, we confirm that CpG-rich genes are highly expressed in germline whereas CpG-poor genes are in a silent state. We further show that, whether tissue-specific or broadly expressed (housekeeping genes), the CpG-rich genes are over-represented close to the replication skew domain borders suggesting some coordination of replication and transcription. We also reveal that the transcription of the longest CpG-rich genes is co-oriented with replication fork progression so that the promoter of these transcriptionally active genes be located into the accessible open chromatin environment surrounding the master replication origins that border the replication skew domains. The observation of a similar gene organization in the mouse genome confirms the interplay of replication, transcription and chromatin structure as the cornerstone of mammalian genome architecture.

Published online:
DOI: 10.1016/j.crme.2012.10.023
Keywords: Gene organization, Replication domains, Gene length, Chromatin structure

Lamia Zaghloul 1, 2; Antoine Baker 1, 2; Benjamin Audit 1, 2; Alain Arneodo 1, 2

1 Université de Lyon, 69000 Lyon, France
2 Laboratoire de Physique, ENS de Lyon, CNRS, 46, allée dʼItalie, 69007 Lyon, France
     author = {Lamia Zaghloul and Antoine Baker and Benjamin Audit and Alain Arneodo},
     title = {Gene organization inside replication domains in mammalian genomes},
     journal = {Comptes Rendus. M\'ecanique},
     pages = {745--757},
     publisher = {Elsevier},
     volume = {340},
     number = {11-12},
     year = {2012},
     doi = {10.1016/j.crme.2012.10.023},
     language = {en},
AU  - Lamia Zaghloul
AU  - Antoine Baker
AU  - Benjamin Audit
AU  - Alain Arneodo
TI  - Gene organization inside replication domains in mammalian genomes
JO  - Comptes Rendus. Mécanique
PY  - 2012
SP  - 745
EP  - 757
VL  - 340
IS  - 11-12
PB  - Elsevier
DO  - 10.1016/j.crme.2012.10.023
LA  - en
ID  - CRMECA_2012__340_11-12_745_0
ER  - 
%0 Journal Article
%A Lamia Zaghloul
%A Antoine Baker
%A Benjamin Audit
%A Alain Arneodo
%T Gene organization inside replication domains in mammalian genomes
%J Comptes Rendus. Mécanique
%D 2012
%P 745-757
%V 340
%N 11-12
%I Elsevier
%R 10.1016/j.crme.2012.10.023
%G en
%F CRMECA_2012__340_11-12_745_0
Lamia Zaghloul; Antoine Baker; Benjamin Audit; Alain Arneodo. Gene organization inside replication domains in mammalian genomes. Comptes Rendus. Mécanique, Volume 340 (2012) no. 11-12, pp. 745-757. doi : 10.1016/j.crme.2012.10.023.

[1] B. Alberts Essential Cell Biology: An Introduction to the Molecular Biology of the Cell, Garland Publishing, 1998

[2] E. Couturier; E.P.C. Rocha Replication-associated gene dosage effects shape the genomes of fast-growing bacteria but only for transcription and translation genes, Mol. Microbiol., Volume 59 (2006), pp. 1506-1518

[3] E.P.C. Rocha; A. Danchin Gene essentiality determines chromosome organisation in bacteria, Nucleic Acids Res., Volume 31 (2003), pp. 6570-6577

[4] E.P.C. Rocha; A. Danchin Essentiality, not expressiveness, drives gene-strand bias in bacteria, Nat. Genet., Volume 34 (2003), pp. 377-378

[5] E.S. Lander et al. Initial sequencing and analysis of the human genomes, Nature, Volume 409 (2001), pp. 860-921

[6] Mouse Genome Sequencing Consortium Initial sequencing and comparative analysis of the mouse genome, Nature, Volume 420 (2002), pp. 520-562

[7] G. Bernardi; B. Olofsson; J. Filipski; M. Zerial; J. Salinas; G. Cuny; M. Meunier-Rotival; F. Rodier The mosaic genome of warm-blooded vertebrates, Science, Volume 228 (1985), pp. 953-958

[8] D. Mouchiroud; G. DʼOnofrio; B. Aïssani; G. Macaya; C. Gautier; G. Bernardi The distribution of genes in the human genome, Gene, Volume 100 (1991), pp. 181-187

[9] G. Bernardi Isochores and the evolutionary genomics of vertebrates, Gene, Volume 241 (2000), pp. 3-17

[10] M.J. Lercher; A.O. Urrutia; A. Pavlicek; L.D. Hurst A unification of mosaic structures in the human genome, Hum. Mol. Genet., Volume 12 (2003), pp. 2411-2415

[11] E.-B. Brodie of Brodie; S. Nicolay; M. Touchon; B. Audit; Y. dʼAubenton-Carafa; C. Thermes; A. Arneodo From DNA sequence analysis to modeling replication in the human genome, Phys. Rev. Lett., Volume 94 (2005), p. 248103

[12] M. Touchon; S. Nicolay; B. Audit; E.-B. Brodie of Brodie; Y. dʼAubenton-Carafa; A. Arneodo; C. Thermes Replication-associated strand asymmetries in mammalian genomes: Toward detection of replication origins, Proc. Natl. Acad. Sci. USA, Volume 102 (2005), pp. 9836-9841

[13] A. Baker; S. Nicolay; L. Zaghloul; Y. dʼAubenton-Carafa; C. Thermes; B. Audit; A. Arneodo Wavelet-based method to disentangle transcription- and replication-associated strand asymmetries in mammalian genomes, Appl. Comput. Harmon. Anal., Volume 28 (2010), pp. 150-170

[14] A. Arneodo; C. Vaillant; B. Audit; F. Argoul; Y. dʼAubenton-Carafa; C. Thermes Multi-scale coding of genomic information: From DNA sequence to genome structure and function, Phys. Rep., Volume 498 (2011), pp. 45-188

[15] M. Huvet; S. Nicolay; M. Touchon; B. Audit; Y. dʼAubenton-Carafa; A. Arneodo; C. Thermes Human gene organization driven by the coordination of replication and transcription, Genome Res., Volume 17 (2007), pp. 1278-1285

[16] B. Audit; S. Nicolay; M. Huvet; M. Touchon; Y. dʼAubenton Carafa; C. Thermes; A. Arneodo DNA replication timing data corroborate in silico human replication origin predictions, Phys. Rev. Lett., Volume 99 (2007), p. 248102

[17] C.-L. Chen; L. Duquenne; B. Audit; G. Guilbaud; A. Rappailles; A. Baker; M. Huvet; Y. dʼAubenton Carafa; O. Hyrien; A. Arneodo; C. Thermes Replication-associated mutational asymmetry in the human genome, Mol. Biol. Evol., Volume 28 (2011), pp. 2327-2337

[18] A. Baker; B. Audit; C.-L. Chen; B. Moindrot; A. Leleu; G. Guilbaud; A. Rappailles; C. Vaillant; A. Goldar; F. Mongelard; Y. dʼAubenton-Carafa; O. Hyrien; C. Thermes; A. Arneodo Replication fork polarity gradients revealed by megabase-sized U-shaped replication timing domains in human cell lines, PLoS Comput. Biol., Volume 8 (2012), p. e1002443

[19] A. Baker; H. Julienne; C.-L. Chen; B. Audit; Y. dʼAubenton Carafa; C. Thermes; A. Arneodo Linking the DNA strand asymmetry to the spatio-temporal replication program. I. About the role of the replication fork polarity in genome evolution, Eur. Phys. E, Volume 35 (2012), p. 92

[20] A. Baker, C.-L. Chen, H. Julienne, B. Audit, Y. dʼAubenton Carafa, C. Thermes, A. Arneodo, Linking the DNA strand asymmetry to the spatio-temporal replication program. II. Accounting for neighbor-dependent substitution rates, Eur. Phys. E (2012), in press.

[21] P. St-Jean; C. Vaillant; B. Audit; A. Arneodo Spontaneous emergence of sequence-dependent rosettelike folding of chromatin fiber, Phys. Rev. E, Volume 77 (2008), p. 061923

[22] B. Audit; L. Zaghloul; C. Vaillant; G. Chevereau; Y. dʼAubenton-Carafa; C. Thermes; A. Arneodo Open chromatin encoded in DNA sequence is the signature of “master” replication origins in human cells, Nucleic Acids Res., Volume 37 (2009), pp. 6064-6075

[23] D. Karolchik; R. Baertsch; M. Diekhans; T.S. Furey; A. Hinrichs; Y.T. Lu; K.M. Roskin; M. Schwartz; C.W. Sugnet; D.J. Thomas; R.J. Weber; D. Haussler; W.J. Kent The UCSC genome browser database, Nucleic Acids Res., Volume 31 (2003), pp. 51-54

[24] M. Touchon; S. Nicolay; A. Arneodo; Y. dʼAubenton-Carafa; C. Thermes Transcription-coupled TA and GC strand asymmetries in the human genome, FEBS Lett., Volume 555 (2003), pp. 579-582

[25] M. Touchon; A. Arneodo; Y. dʼAubenton-Carafa; C. Thermes Transcription-coupled and splicing-coupled strand asymmetries in eukaryotic genomes, Nucleic Acids Res., Volume 32 (2004), pp. 4969-4978

[26] S. Nicolay; E.-B. Brodie of Brodie; M. Touchon; Y. dʼAubenton-Carafa; C. Thermes; A. Arneodo From scale invariance to deterministic chaos in DNA sequences: Towards a deterministic description of gene organization in the human genome, Physica A, Volume 342 (2004), pp. 270-280

[27] S. Nicolay; F. Argoul; M. Touchon; Y. dʼAubenton-Carafa; C. Thermes; A. Arneodo Low frequency rhythms in human DNA sequences: A key to the organization of gene location and orientation?, Phys. Rev. Lett., Volume 93 (2004), p. 108101

[28] S. Nicolay; E.B. Brodie of Brodie; M. Touchon; B. Audit; Y. dʼAubenton-Carafa; C. Thermes; A. Arneodo Bifractality of human DNA strand-asymmetry profiles results from transcription, Phys. Rev. E, Volume 75 (2007), p. 032902

[29] L. Zaghloul, Transcriptional activity, chromatin state and replication timing in domains of compositional skew in the human genome, Ph.D. thesis, Université de Lyon, Ecole Normale Supérieure de Lyon, 2009.

[30] M. Sémon; J.R. Lobry; L. Duret No evidence for tissue-specific adaptation of synonymous codon usage in humans, Mol. Biol. Evol., Volume 23 (2006), pp. 523-529

[31] M. Sémon; L. Duret Evolutionary origin and maintenance of coexpressed gene clusters in mammals, Mol. Biol. Evol., Volume 23 (2006), pp. 1715-1723

[32] A.I. Su; T. Wiltshire; S. Batalov; H. Lapp; K.A. Ching; D. Block; J. Zhang; R. Soden; M. Hayakawa; G. Kreiman; M.P. Cooke; J.R. Walker; J.B. Hogenesch A gene atlas of the mouse and human protein-encoding transcriptomes, Proc. Natl. Acad. Sci. USA, Volume 101 (2004), pp. 6062-6067

[33] F. Chalmel; A.D. Rolland; C. Niederhauser-Wiederkehr; S.S.W. Chung; P. Demougin; A. Gattiker; J. Moore; J.-J. Patard; D.J. Wolgemuth; B. Jégou; M. Primig The conserved transcriptome in human and rodent male gametogenesis, Proc. Natl. Acad. Sci. USA, Volume 104 (2007), pp. 8346-8351

[34] M.M. Suzuki; A. Bird DNA methylation landscapes: Provocative insights from epigenomics, Nat. Rev. Genet., Volume 9 (2008), pp. 465-476

[35] D.N. Cooper; M.H. Taggart; A.P. Bird Unmethylated domains in vertebrate DNA, Nucleic Acids Res., Volume 11 (1983), pp. 647-658

[36] A. Bird; M. Taggart; M. Frommer; O.J. Miller; D. Macleod A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA, Cell, Volume 40 (1985), pp. 91-99

[37] M. Gardiner-Garden; M. Frommer CpG islands in vertebrate genomes, J. Mol. Biol., Volume 196 (1987), pp. 261-282

[38] F. Antequera; A. Bird Number of CpG islands and genes in human and mouse, Proc. Natl. Acad. Sci. USA, Volume 90 (1993), pp. 11995-11999

[39] D. Macleod; R.R. Ali; A. Bird An alternative promoter in the mouse major histocompatibility complex class II I-Abeta gene: Implications for the origin of CpG islands, Mol. Cell. Biol., Volume 18 (1998), pp. 4433-4443

[40] L. Ponger; L. Duret; D. Mouchiroud Determinants of CpG islands: Expression in early embryo and isochore structure, Genome Res., Volume 11 (2001), pp. 1854-1860

[41] F. Antequera Structure, function and evolution of CpG island promoters, Cell. Mol. Life Sci., Volume 60 (2003), pp. 1647-1658

[42] S. Delgado; M. Gómez; A. Bird; F. Antequera Initiation of DNA replication at CpG islands in mammalian chromosomes, EMBO J., Volume 17 (1998), pp. 2426-2435

[43] F. Antequera; A. Bird CpG islands as genomic footprints of promoters that are associated with replication origins, Curr. Biol., Volume 9 (1999), p. R661-R667

[44] J.-C. Cadoret; F. Meisch; V. Hassan-Zadeh; I. Luyten; C. Guillet; L. Duret; H. Quesneville; M.-N. Prioleau Genome-wide studies highlight indirect links between human replication origins and gene regulation, Proc. Natl. Acad. Sci. USA, Volume 105 (2008), pp. 15837-15842

[45] J. Sequeira-Mendes; R. Diaz-Uriarte; A. Apedaile; D. Huntley; N. Brockdorff; M. Gomez Transcription initiation activity sets replication origin efficiency in mammalian cells, PLoS Genet., Volume 5 (2009), p. e1000446

[46] A. Necsulea; C. Guillet; J.-C. Cadoret; M.-N. Prioleau; L. Duret The relationship between DNA replication and human genome organization, Mol. Biol. Evol., Volume 26 (2009), pp. 729-741

[47] D. Takai; P.A. Jones Comprehensive analysis of CpG islands in human chromosomes 21 and 22, Proc. Natl. Acad. Sci. USA, Volume 99 (2002), pp. 3740-3745

[48] S. Saxonov; P. Berg; D.L. Brutlag A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters, Proc. Natl. Acad. Sci. USA, Volume 103 (2006), pp. 1412-1417

[49] M. Weber; I. Hellmann; M.B. Stadler; L. Ramos; S. Pääbo; M. Rebhan; D. Schübeler Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome, Nat. Genet., Volume 39 (2007), pp. 457-466

[50] C.S.M. Tang; R.J. Epstein A structural split in the human genome, PLoS One, Volume 2 (2007), p. e603

[51] F. Mohn; D. Schübeler Genetics and epigenetics: Stability and plasticity during cellular differentiation, Trends Genet., Volume 25 (2009), pp. 129-136

[52] P. Carninci; A. Sandelin; B. Lenhard; S. Katayama; K. Shimokawa; J. Ponjavic; C.A.M. Semple; M.S. Taylor; P.G. Engström; M.C. Frith; A.R.R. Forrest; W.B. Alkema; S.L. Tan; C. Plessy; R. Kodzius; T. Ravasi; T. Kasukawa; S. Fukuda; M. Kanamori-Katayama; Y. Kitazume; H. Kawaji; C. Kai; M. Nakamura; H. Konno; K. Nakano; S. Mottagui-Tabar; P. Arner; A. Chesi; S. Gustincich; F. Persichetti; H. Suzuki; S.M. Grimmond; C.A. Wells; V. Orlando; C. Wahlestedt; E.T. Liu; M. Harbers; J. Kawai; V.B. Bajic; D.A. Hume; Y. Hayashizaki Genome-wide analysis of mammalian promoter architecture and evolution, Nat. Genet., Volume 38 (2006), pp. 626-635

[53] B. Aïssani; G. Bernardi CpG islands, genes and isochores in the genomes of vertebrates, Gene, Volume 106 (1991), pp. 185-195

[54] C. Lemaitre; L. Zaghloul; M.-F. Sagot; C. Gautier; A. Arneodo; E. Tannier; B. Audit Analysis of fine-scale mammalian evolutionary breakpoints provides new insight into their relation to genome organisation, BMC Genomics, Volume 10 (2009), p. 335

[55] F. Larsen; G. Gundersen; R. Lopez; H. Prydz CpG islands as gene markers in the human genome, Genomics, Volume 13 (1992), pp. 1095-1107

[56] C.I. Castillo-Davis; S.L. Mekhedov; D.L. Hartl; E.V. Koonin; F.A. Kondrashov Selection for short introns in highly expressed genes, Nat. Genet., Volume 31 (2002), pp. 415-418

[57] E. Eisenberg; E.Y. Levanon Human housekeeping genes are compact, Trends Genet., Volume 19 (2003), pp. 362-365

[58] A.O. Urrutia; L.D. Hurst The signature of selection mediated by expression on human genes, Genome Res., Volume 13 (2003), pp. 2260-2264

[59] L. Duret; D. Mouchiroud; C. Gautier Statistical analysis of vertebrate sequences reveals that long genes are scarce in GC-rich isochores, J. Mol. Evol., Volume 40 (1995), pp. 308-317

[60] M. Ebisuya; T. Yamamoto; M. Nakajima; E. Nishida Ripples from neighbouring transcription, Nat. Cell Biol., Volume 10 (2008), pp. 1106-1113

[61] N.N. Batada; L.D. Hurst Evolution of chromosome organization driven by selection for reduced gene expression noise, Nat. Genet., Volume 39 (2007), pp. 945-949

[62] F. Mohn; M. Weber; M. Rebhan; T.C. Roloff; J. Richter; M.B. Stadler; M. Bibel; D. Schübeler Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors, Mol. Cell, Volume 30 (2008), pp. 755-766

[63] C.R. Farthing; G. Ficz; R.K. Ng; C.-F. Chan; S. Andrews; W. Dean; M. Hemberger; W. Reik Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes, PLoS Genet., Volume 4 (2008), p. e1000116

[64] N. Arnheim; P. Calabrese Understanding what determines the frequency and pattern of human germline mutations, Nat. Rev. Genet., Volume 10 (2009), pp. 478-488

[65] R. Illingworth; A. Kerr; D. Desousa; H. Jorgensen; P. Ellis; J. Stalker; D. Jackson; C. Clee; R. Plumb; J. Rogers; S. Humphray; T. Cox; C. Langford; A. Bird A novel CpG island set identifies tissue-specific methylation at developmental gene loci, PLoS Biol., Volume 6 (2008), p. e22

[66] K. Woodfine; D.M. Beare; K. Ichimura; S. Debernardi; A.J. Mungall; H. Fiegler; V.P. Collins; N.P. Carter; I. Dunham Replication timing of human chromosome 6, Cell Cycle, Volume 4 (2005), pp. 172-176

[67] R. Desprat; D. Thierry-Mieg; N. Lailler; J. Lajugie; C. Schildkraut; J. Thierry-Mieg; E.E. Bouhassira Predictable dynamic program of timing of DNA replication in human cells, Genome Res., Volume 19 (2009), pp. 2288-2299

[68] C.-L. Chen; A. Rappailles; L. Duquenne; M. Huvet; G. Guilbaud; L. Farinelli; B. Audit; Y. dʼAubenton-Carafa; A. Arneodo; O. Hyrien; C. Thermes Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes, Genome Res., Volume 4 (2010), pp. 447-457

[69] R.S. Hansen; S. Thomas; R. Sandstrom; T.K. Canfield; R.E. Thurman; M. Weaver; M.O. Dorschner; S.M. Gartler; J.A. Stamatoyannopoulos Sequencing newly replicated DNA reveals widespread plasticity in human replication timing, Proc. Natl. Acad. Sci. USA, Volume 107 (2010), pp. 139-144

[70] S. Farkash-Amar; D. Lipson; A. Polten; A. Goren; C. Helmstetter; Z. Yakhini; I. Simon Global organization of replication time zones of the mouse genome, Genome Res., Volume 18 (2008), pp. 1562-1570

[71] I. Hiratani; T. Ryba; M. Itoh; T. Yokochi; M. Schwaiger; C.-W. Chang; Y. Lyou; T.M. Townes; D. Schubeler; D.M. Gilbert Global reorganization of replication domains during embryonic stem cell differentiation, PLoS Biol., Volume 6 (2008), p. e245

[72] T. Ryba; I. Hiratani; J. Lu; M. Itoh; M. Kulik; J. Zhang; T.C. Schulz; A.J. Robins; S. Dalton; D.M. Gilbert Evolutionarily conserved replication timing profiles predict long-range chromatin interactions and distinguish closely related cell types, Genome Res., Volume 20 (2010), pp. 761-770

[73] I. Hiratani; T. Ryba; M. Itoh; J. Rathjen; M. Kulik; B. Papp; E. Fussner; D.P. Bazett-Jones; K. Plath; S. Dalton; P.D. Rathjen; D.M. Gilbert Genome-wide dynamics of replication timing revealed by in vitro models of mouse embryogenesis, Genome Res., Volume 20 (2010), pp. 155-169

[74] A. Baker; B. Audit; S.C.-H. Yang; J. Bechhoefer; A. Arneodo Inferring where and when replication initiates from genome-wide replication timing data, Phys. Rev. Lett., Volume 108 (2012), p. 268101

[75] B. Audit, A. Baker, C.-L. Chen, A. Rappailles, G. Guilbaud, H. Julienne, A. Goldar, Y. dʼAubenton-Carafa, O. Hyrien, C. Thermes, A. Arneodo, Multi-scale analysis of genome wide replication timing profiles using a wavelet-based signal-processing algorithm, Nat. Protoc. (2012), in press.

[76] B. Moindrot; B. Audit; P. Klous; A. Baker; C. Thermes; W. de Laat; P. Bouvet; F. Mongelard; A. Arneodo 3D chromatin conformation correlates with replication timing and is conserved in resting cells, Nucleic Acids Res., Volume 40 (2012), pp. 9470-9481

[77] O. Hyrien; A. Goldar Mathematical modelling of eukaryotic DNA replication, Chromosome Res., Volume 18 (2010), pp. 147-161

[78] G. Guilbaud; A. Rappailles; A. Baker; C.-L. Chen; A. Arneodo; A. Goldar; Y. dʼAubenton-Carafa; C. Thermes; B. Audit; O. Hyrien Evidence for sequential and increasing activation of replication origins along replication timing gradients in the human genome, PLoS Comput. Biol., Volume 7 (2011), p. e1002322

Cited by Sources:

Comments - Policy