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PMID: 15105447 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Heterochromatin on the inactive X chromosome delays replication timing without affecting origin usage.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 18 ·2004-05-04 ·Pages 6923-8

Gómez M, Brockdorff N

Abstract

DNA replication origins (ORIs) map close to promoter regions in many organisms, including mammals. However, the relationship between initiation of replication and transcription is not well understood. To address this issue, we have analyzed replication timing and activity of several CpG island-associated ORIs on the transcriptionally active and silent X chromosomes. We find equivalent ORI usage and efficiency of both alleles at sites that are replicated late on the inactive X chromosome. Thus, in contrast to its repressive effect on transcription, heterochromatin does not influence ORI activity. These findings suggest that the relationship between sites of transcription and replication initiation at CpG island regions is restricted to early development, and that subsequent gene silencing and heterochromatin formation influence only the timing of ORI activation.

MeSH Terms
Animals CpG Islands/physiology Dosage Compensation, Genetic Female Heterochromatin Mice Replication Origin/physiology Transcription, Genetic X Chromosome
Chemicals
Heterochromatin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Gómez María
X Inactivation Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College for Science, Technology, and Medicine, Hammersmith Hospital, DuCane Road, London W12 0NN, United Kingdom.
Brockdorff Neil
References (65)
65 references, click to expand
  1. An Abf1p C-terminal region lacking transcriptional activation potential stimulates a yeast origin of replication.
    Nucleic Acids Res. 1997 Nov 1;25(21):4250-6 PMID: 9336454
  2. Differential replication timing of X-linked genes measured by a novel method using single-nucleotide primer extension.
    Nucleic Acids Res. 1998 Jan 15;26(2):684-6 PMID: 9421536
  3. Replication initiation point mapping.
    Methods. 1997 Nov;13(3):271-80 PMID: 9441853
  4. Mapping replication origins by quantifying relative abundance of nascent DNA strands using competitive polymerase chain reaction.
    Methods. 1997 Nov;13(3):301-12 PMID: 9441856
  5. Activation of chromosomal DNA replication in Saccharomyces cerevisiae by acidic transcriptional activation domains.
    Mol Cell Biol. 1998 Mar;18(3):1296-302 PMID: 9488444
  6. Initiation of DNA replication at CpG islands in mammalian chromosomes.
    EMBO J. 1998 Apr 15;17(8):2426-35 PMID: 9545253
  7. Specification of regions of DNA replication initiation during embryogenesis in the 65-kilobase DNApolalpha-dE2F locus of Drosophila melanogaster.
    Mol Cell Biol. 1999 Jan;19(1):547-55 PMID: 9858578
  8. Replication origins in metazoan chromosomes: fact or fiction?
    Bioessays. 1999 Jan;21(1):5-16 PMID: 10070250
  9. Tsix, a gene antisense to Xist at the X-inactivation centre.
    Nat Genet. 1999 Apr;21(4):400-4 PMID: 10192391
  10. The one-kilobase DNA fragment upstream of the ardC actin gene of Physarum polycephalum is both a replicator and a promoter.
    Mol Cell Biol. 1999 May;19(5):3506-14 PMID: 10207074
  11. The timing of XIST replication: dominance of the domain.
    Hum Mol Genet. 1999 Jun;8(6):1085-9 PMID: 10332041
  12. The pattern of replication at a human telomeric region (16p13.3): its relationship to chromosome structure and gene expression.
    Hum Mol Genet. 1999 Aug;8(8):1373-86 PMID: 10400984
  13. An origin of bidirectional DNA replication is located within a CpG island at the 3" end of the chicken lysozyme gene.
    Nucleic Acids Res. 1999 Aug 1;27(15):3009-17 PMID: 10454594
  14. CpG islands as genomic footprints of promoters that are associated with replication origins.
    Curr Biol. 1999 Sep 9;9(17):R661-7 PMID: 10508580
  15. Organization of DNA replication origins in the fission yeast genome.
    EMBO J. 1999 Oct 15;18(20):5683-90 PMID: 10523311
  16. Gene action in the X-chromosome of the mouse (Mus musculus L.).
    Nature. 1961 Apr 22;190:372-3 PMID: 13764598
  17. Promoter-specific hypoacetylation of X-inactivated genes.
    Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13825-30 PMID: 10570157
  18. Replication origins of mammalian chromosomes: the happy few.
    Front Biosci. 1999 Dec 1;4:D859-68 PMID: 10577395
  19. Long-distance control of origin choice and replication timing in the human beta-globin locus are independent of the locus control region.
    Mol Cell Biol. 2000 Aug;20(15):5581-91 PMID: 10891496
  20. Disruption of imprinted X inactivation by parent-of-origin effects at Tsix.
    Cell. 2000 Sep 29;103(1):17-27 PMID: 11051544
  21. Escape from gene silencing in ICF syndrome: evidence for advanced replication time as a major determinant.
    Hum Mol Genet. 2000 Nov 1;9(18):2575-87 PMID: 11063717
  22. Methylation profiles of DXPas34 during the onset of X-inactivation.
    Hum Mol Genet. 2001 Jan 1;10(1):31-8 PMID: 11136711
  23. DNA replication control through interaction of E2F-RB and the origin recognition complex.
    Nat Cell Biol. 2001 Mar;3(3):289-95 PMID: 11231579
  24. A novel DNA replication origin identified in the human heat shock protein 70 gene promoter.
    Mol Cell Biol. 1994 Sep;14(9):6386-97 PMID: 8065368
  25. A sensitive, quantitative assay for measurement of allele-specific transcripts differing by a single nucleotide.
    PCR Methods Appl. 1992 Feb;1(3):160-3 PMID: 1282066
  26. Initiation zone of DNA replication at the aldolase B locus encompasses transcription promoter region.
    Nucleic Acids Res. 1994 Dec 11;22(24):5385-90 PMID: 7816629
  27. Reverse replication timing for the XIST gene in human fibroblasts.
    Hum Mol Genet. 1995 May;4(5):813-20 PMID: 7633440
  28. Participation of the human beta-globin locus control region in initiation of DNA replication.
    Science. 1995 Nov 3;270(5237):815-9 PMID: 7481774
  29. Allele-specific replication timing in imprinted domains: absence of asynchrony at several loci.
    Hum Mol Genet. 1995 Dec;4(12):2287-93 PMID: 8634700
  30. DNA hypomethylation can activate Xist expression and silence X-linked genes.
    Genes Dev. 1996 Aug 15;10(16):1991-2002 PMID: 8769643
  31. Tissue and lineage-specific variation in inactive X chromosome expression of the murine Smcx gene.
    Hum Mol Genet. 1996 Sep;5(9):1361-6 PMID: 8872478
  32. A variable domain of delayed replication in FRAXA fragile X chromosomes: X inactivation-like spread of late replication.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4587-92 PMID: 9114034
  33. X chromosome inactivation is mediated by Xist RNA stabilization.
    Cell. 1997 Sep 5;90(5):907-16 PMID: 9298902
  34. Stabilization of Xist RNA mediates initiation of X chromosome inactivation.
    Cell. 1997 Oct 3;91(1):99-107 PMID: 9335338
  35. Regulation of imprinted X-chromosome inactivation in mice by Tsix.
    Development. 2001 Apr;128(8):1275-86 PMID: 11262229
  36. DNA replication origins: from sequence specificity to epigenetics.
    Nat Rev Genet. 2001 Aug;2(8):640-5 PMID: 11483989
  37. Developmental regulation of DNA replication timing at the human beta globin locus.
    EMBO J. 2001 Nov 1;20(21):6150-7 PMID: 11689454
  38. RNA polymerase II and III transcription factors can stimulate DNA replication by modifying origin chromatin structures.
    Nucleic Acids Res. 2001 Nov 15;29(22):4570-80 PMID: 11713306
  39. Methylation of histone H3 at Lys-9 is an early mark on the X chromosome during X inactivation.
    Cell. 2001 Dec 14;107(6):727-38 PMID: 11747809
  40. Differentially methylated forms of histone H3 show unique association patterns with inactive human X chromosomes.
    Nat Genet. 2002 Jan;30(1):73-6 PMID: 11740495
  41. Identification of a binding region for human origin recognition complex proteins 1 and 2 that coincides with an origin of DNA replication.
    Mol Cell Biol. 2002 Feb;22(4):1036-48 PMID: 11809796
  42. Mapping of an origin of DNA replication near the transcriptional promoter of the human HPRT gene.
    J Cell Biochem. 2002;85(2):346-56 PMID: 11948690
  43. Control of replication timing by a transcriptional silencer.
    Curr Biol. 2002 Jun 4;12(11):869-75 PMID: 12062049
  44. The origin recognition complex marks a replication origin in the human TOP1 gene promoter.
    J Biol Chem. 2002 Aug 30;277(35):31430-40 PMID: 12004060
  45. Xist RNA and the mechanism of X chromosome inactivation.
    Annu Rev Genet. 2002;36:233-78 PMID: 12429693
  46. Histone acetylation regulates the time of replication origin firing.
    Mol Cell. 2002 Nov;10(5):1223-33 PMID: 12453428
  47. Same origins of DNA replication function on the active and inactive human X chromosomes.
    J Cell Biochem. 2003 Apr 1;88(5):923-31 PMID: 12616531
  48. Asynchronous replication timing of imprinted loci is independent of DNA methylation, but consistent with differential subnuclear localization.
    Genes Dev. 2003 Mar 15;17(6):759-73 PMID: 12651894
  49. Replication of the chicken beta-globin locus: early-firing origins at the 5' HS4 insulator and the rho- and betaA-globin genes show opposite epigenetic modifications.
    Mol Cell Biol. 2003 May;23(10):3536-49 PMID: 12724412
  50. Heritable gene silencing in lymphocytes delays chromatid resolution without affecting the timing of DNA replication.
    Nat Cell Biol. 2003 Jul;5(7):668-74 PMID: 12833066
  51. Replication of alpha and beta globin DNA sequences occurs during early S phase in murine erythroleukemia cells.
    Proc Natl Acad Sci U S A. 1981 May;78(5):3058-62 PMID: 6942415
  52. Replication of animal mitochondrial DNA.
    Cell. 1982 Apr;28(4):693-705 PMID: 6178513
  53. Asynchronous replication of homologous loci on human active and inactive X chromosomes.
    Proc Natl Acad Sci U S A. 1990 May;87(10):3685-9 PMID: 2339112
  54. An initiation zone of chromosomal DNA replication located upstream of the c-myc gene in proliferating HeLa cells.
    Mol Cell Biol. 1990 Sep;10(9):4899-904 PMID: 2201906
  55. Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome.
    Nature. 1991 May 23;351(6324):329-31 PMID: 2034279
  56. Chromatin differences between active and inactive X chromosomes revealed by genomic footprinting of permeabilized cells using DNase I and ligation-mediated PCR.
    Genes Dev. 1991 Jun;5(6):1102-13 PMID: 2044957
  57. A yeast chromosomal origin of DNA replication defined by multiple functional elements.
    Science. 1992 Feb 14;255(5046):817-23 PMID: 1536007
  58. Role of multifunctional autonomously replicating sequence binding factor 1 in the initiation of DNA replication and transcriptional control in Saccharomyces cerevisiae.
    Mol Cell Biol. 1992 Mar;12(3):1064-77 PMID: 1545789
  59. Expression of Xist during mouse development suggests a role in the initiation of X chromosome inactivation.
    Cell. 1993 Jan 29;72(2):171-82 PMID: 8425217
  60. Association of fragile X syndrome with delayed replication of the FMR1 gene.
    Cell. 1993 Jul 2;73(7):1403-9 PMID: 8324827
  61. Role for DNA methylation in genomic imprinting.
    Nature. 1993 Nov 25;366(6453):362-5 PMID: 8247133
  62. Replication structure of the human beta-globin gene domain.
    Nature. 1993 Dec 9;366(6455):588-90 PMID: 8255298
  63. Number of CpG islands and genes in human and mouse.
    Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11995-9 PMID: 7505451
  64. Evidence that random and imprinted Xist expression is controlled by preemptive methylation.
    Cell. 1994 Apr 8;77(1):41-51 PMID: 8156596
  65. Fine mapping of a replication origin of human DNA.
    Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7119-23 PMID: 8041756
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0401854101
Published
2004-05-04
Epub
2004-00-22
Pages
6923-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC406443
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0401854101 PMC Full Text View journal details
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