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Domain organization of allele–specific replication within the GABRB3 gene cluster requires a biparental 15q11–13 contribution

Abstract

Imprinting marks the parental origin of chromosomes, resulting in allele–specific changes in chromatin organization, transcription and replication. We report a 50–60 kb domain of allele–specific replication between the γ–aminobutyric acid receptor subunit β3 (GABRB3) and α5 (GABRA5) genes. Replication of this domain occurs in early S phase on the maternal chromosome 15 but is delayed until the end of S phase on the paternal homologue. In contrast, the genomic regions flanking this domain exhibit paternal earlier replication in mid to late S phase. Uniparental disomy or hemizygous deletion of chromosome 15 results in altered allele–specific replication kinetics compared with normals, suggesting that allele–specific replication within the GABRB3/A5 region may be regulated by reciprocal imprints on the maternal and paternal chromosomes.

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References

  1. Crouse, H.V. The controlling element in sex chromosome behavior in Sciara. Genetics 45, 1429–1443 (1960).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. McGrath, J. & Solter, D. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37, 179–183 (1984).

    Article  CAS  PubMed  Google Scholar 

  3. Surani, M.A.H., Barton, S.C. & Norris, M.L. Development of reconstituted mouse eggs suggests Imprinting of the genome during gametogenesis. Nature 308, 548–550 (1984).

    Article  CAS  PubMed  Google Scholar 

  4. Barlow, D.P., Stoger, R., Herrmann, B.G., Saito, K. & Schweifer, N. The mouse Insulin-like growth factor type-2 receptor Is Imprinted and closely linked to the Time locus. Nature 349, 84–87 (1991).

    Article  CAS  PubMed  Google Scholar 

  5. Bartolomei, M.S., Zemel, S. & Tilghman, S.M. Parental imprinting of the mouse H19 gene. Nature 351, 153–155 (1991).

    Article  CAS  PubMed  Google Scholar 

  6. DeChlara, T.M., Robertson, E.J. & Efstratiadis, A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64, 849–859 (1991).

    Article  Google Scholar 

  7. Rainier, S. et al. Relaxation of Imprinted genes in human cancer. Nature 362, 747–749 (1993).

    Article  CAS  PubMed  Google Scholar 

  8. Ohisson, R. et al. Igf2 is parentally imprinted during human embryogenesis and in the Beckwlth-Wiedemann syndrome. Nature Genet. 4, 94–97 (1993).

    Article  Google Scholar 

  9. Zhang, Y. & Tyko, B. Monoalleleic expression of the human H19 gene. Nature Genet. 1, 40–44 (1992).

    Article  CAS  PubMed  Google Scholar 

  10. Butler, M.G. & Palmer, C.G. Parental origin of chromosome 15 deletion In Prader-Willl syndrome. Lancet i, 1285–1286 (1983).

    Article  Google Scholar 

  11. Nicholls, R.D., Knoll, J.H.M., Butler, M.G., Karam, S. & Lalande, M. Genetic imprinting suggested by maternal heterodisomy in non-deletion Prader-Willl syndrome. Nature 342, 281–285 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Knoll, J.H.M. et al. Angelman and Prader-Willl syndromes share a common chromosome 15 deletion but differ In parental origin of the deletion. Am. J. Med. Genet. 32, 285–290 (1989).

    Article  CAS  PubMed  Google Scholar 

  13. Malcolm, S. et al. Uniparental paternal disomy In Angelman's syndrome. Lancet 337, 694–697 (1991).

    Article  CAS  PubMed  Google Scholar 

  14. Wagstaff, J. et al. Maternal but not paternal transmission of 15q11-13-llnked nondeletion Angelman syndrome leads to phenotypic expression. Nature Genet. 1, 291–294 (1992).

    Article  CAS  PubMed  Google Scholar 

  15. Cattanach, B.M. et al. A candidate mouse model for Prader-Willi syndrome which shows an absence of Snrpn expression. Nature Genet. 2, 270–274 (1992).

    Article  CAS  PubMed  Google Scholar 

  16. Leff, S.E. et al. Maternal Imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader-Willi syndrome region. Nature Genet. 2, 259–264 (1992).

    Article  CAS  PubMed  Google Scholar 

  17. Özcelik, T. et al. Small nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region. Nature Genet. 2, 265–269 (1992).

    Article  PubMed  Google Scholar 

  18. Reed, M.L. & Leff, S.E. Maternal imprinting of human SNRPN, a gene deleted in Prader-Willi syndrome. Nature Genet. 6, 163–167 (1994).

    Article  CAS  PubMed  Google Scholar 

  19. Sutcliffe, J.S. et al. Deletions of a differentially methylated CpG Island at the SNRPN gene define a putative imprinting control region. Nature Genet. 8, 52–58 (1994).

    Article  CAS  PubMed  Google Scholar 

  20. Wevrick, R., Kerns, J.A. & Franke, U. Identification of a novel paternally expressed gene In the Prader-Willi syndrome region. Hum. molec. Genet. 3, 1877–1882 (1994).

    Article  CAS  PubMed  Google Scholar 

  21. Kitsberg, D. et al. Allele-specific replication timing of Imprinted gene regions. Nature 364, 459–463 (1993).

    Article  CAS  PubMed  Google Scholar 

  22. Knoll, J.H.M., Cheng, S.D. & Lalande, M. Allele specificity of DNA replication timing in the Angelman/Prader-Willi syndrome Imprinted chromosomal region. Nature Genet. 6, 41–45 (1994).

    Article  CAS  PubMed  Google Scholar 

  23. Selig, S., Okumura, K., Ward, D.C. & Cedar, H. Delineation of DNA replication time zones by fluorescence In situ hybridization. EMBO J. 11, 1217–1225 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Torchia, B.S., Call, L.M. & Migeon, B.R. DNA replication analysis of FMR1, XIST, and factor 8C loci by FISH shows nontranscribed X-linked genes replicate late. Am. J. hum. Genet. 55, 96–104 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Boggs, B.A. & Chinault, A.C. Analysis of replication timing properties of human X-chromosomal loci by fluorescence in situ hybridization. Proc. natn. Acad. Sci. U.S.A. 91, 6083–6087 (1994).

    Article  CAS  Google Scholar 

  26. Chess, A., Simon, I., Cedar, H. & Axel, R. Allelic inactivation regulates olfactory receptor gene expression. Cell 78, 823–634 (1994).

    Article  CAS  PubMed  Google Scholar 

  27. Sinnett, D. et al. High-resolution mapping of the g-aminobutyric acid receptor subunit β3 and a5 gene cluster on chromosome 15q11–q13 and localization of breakpoints in two Angelman syndrome patients. Am. J. hum. Genet. 52, 1216–1229 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Hassan, A. & Cook, P.R. Does transcription by RNA polymerase play a direct role In the initiation of replication? J. Cell Sci. 107, 1381–1387 (1994).

    CAS  PubMed  Google Scholar 

  29. Judd, B.H., Allelic cross talk. Cell 53, 841–843 (1988).

    Article  CAS  PubMed  Google Scholar 

  30. Pirrotta, V. Transvection and long-distance gene regulation. BioEssays 12, 409–414 (1990).

    Article  CAS  PubMed  Google Scholar 

  31. Tsai, J.-Y. & Silver, L.M. Escape from genomic imprinting at the mouse T-associated maternal effect (Tme) locus. Genetics 129, 1159–1166 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Latham, K.E., Doherty, A.S., Scott, C.D. & Schultz, R.M. lgf2r and Igf2 gene expression in androgenetic, gynogenetic, and parthenogenetic preimplantation mouse embryos: absence of regulation by genomic imprinting. Genes Dev. 8, 290–299 (1994).

    Article  CAS  PubMed  Google Scholar 

  33. Mutter, G.L., Stewart, C.L., Chaponot, M.L. & Pomponio, R.J., Oppositely Imprinted genes H19 and insulin-like growth factor 2 are coexpressed in human androgenetic trophoblast. Am. J. hum. Genet. 53, 1096–1102 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Kay, G.F., Barton, S.C., Surani, A. & Rastan, S. Imprinting and X chromosome counting mechanisms determine Xist expression in early mouse development. Cell 77, 629–650 (1994).

    Article  Google Scholar 

  35. Barlow, D.P. Imprinting: a gamete's point of view. Trends Genet. 10, 194–199 (1994).

    Article  CAS  PubMed  Google Scholar 

  36. Bottani, A. et al. Angelman syndrome due to paternal uniparental disomy of chromosome 15: A milder phenotype? Am. J. med. Genet. 51, 35–40 (1994).

    Article  CAS  PubMed  Google Scholar 

  37. Robinson, W.P. et al. Nondisjunction of chromosome 15: Origin and recombination. Am. J. hum. Genet. 53, 740–751 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. LaSalle, J.M., Tolentino, P.J., Freeman, G.L., Nadler, L.M. & Hafler, D.A. Early signaling defects in human T cells anergized by T cell presentation of autoantigen. J. exp. Med. 176, 177–186 (1994).

    Article  Google Scholar 

  39. Arndt-Jovin, D.J. & Jovin, T.M. Analysis and sorting of living cells according to deoxyribonucleic acid content. J. histochem. Cytochem. 25, 585–589 (1977).

    Article  CAS  PubMed  Google Scholar 

  40. Crissman, H.A., Hofland, M.H., Stevenson, A.P., Wilder, M.E. & Tobey, R.A. Use of DiO-C5. -3 to Improve Hoechst 33342 uptake resolution of DNA content and survival of CHO cells. Exp. Cell Res. 174, 388–396 (1994).

    Article  Google Scholar 

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LaSalle, J., Lalande, M. Domain organization of allele–specific replication within the GABRB3 gene cluster requires a biparental 15q11–13 contribution. Nat Genet 9, 386–394 (1995). https://doi.org/10.1038/ng0495-386

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