Home LiteratureArticle Details
PMID: 9843980 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A model system to study genomic imprinting of human genes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 25 ·1998-12-08 ·Pages 14857-62

Gabriel JM, Higgins MJ, Gebuhr TC, Shows TB, Saitoh S, Nicholls RD

Abstract

Somatic-cell hybrids have been shown to maintain the correct epigenetic chromatin states to study developmental globin gene expression as well as gene expression on the active and inactive X chromosomes. This suggests the potential use of somatic-cell hybrids containing either a maternal or a paternal human chromosome as a model system to study known imprinted genes and to identify as-yet-unknown imprinted genes. Testing gene expression by using reverse transcription followed by PCR, we show that functional imprints are maintained at four previously characterized 15q11-q13 loci in hybrids containing a single human chromosome 15 and at two chromosome 11p15 loci in hybrids containing a single chromosome 11. In contrast, three gamma-aminobutyric acid type A receptor subunit genes in 15q12-q13 are nonimprinted. Furthermore, we have found that differential DNA methylation imprints at the SNRPN promoter and at a CpG island in 11p15 are also maintained in somatic-cell hybrids. Somatic-cell hybrids therefore are a valid and powerful system for studying known imprinted genes as well as for rapidly identifying new imprinted genes.

MeSH Terms
Chromosomes, Human, Pair 11 Chromosomes, Human, Pair 15 DNA Methylation Gene Expression Genome, Human Genomic Imprinting Humans Models, Genetic X Chromosome
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Gabriel J M
Department of Genetics, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, 10900 Euclid Avenue, Cleveland, OH 44106-4955, USA.
Higgins M J
Gebuhr T C
Shows T B
Saitoh S
Nicholls R D
References (56)
56 references, click to expand
  1. Histone acetylation: facts and questions.
    Chromosoma. 1994 Dec;103(7):441-9 PMID: 7720410
  2. Identification of a novel paternally expressed gene in the Prader-Willi syndrome region.
    Hum Mol Genet. 1994 Oct;3(10):1877-82 PMID: 7849716
  3. Transcriptional activation of the Epstein-Barr virus latency C promoter after 5-azacytidine treatment: evidence that demethylation at a single CpG site is crucial.
    Mol Cell Biol. 1995 Nov;15(11):6150-9 PMID: 7565767
  4. Deficiency of the beta 3 subunit of the type A gamma-aminobutyric acid receptor causes cleft palate in mice.
    Nat Genet. 1995 Nov;11(3):344-6 PMID: 7581464
  5. Uniparental disomy in humans: development of an imprinting map and its implications for prenatal diagnosis.
    Hum Mol Genet. 1995;4 Spec No:1757-64 PMID: 8541876
  6. Gene structure, DNA methylation, and imprinted expression of the human SNRPN gene.
    Am J Hum Genet. 1996 Feb;58(2):335-46 PMID: 8571960
  7. Peg3 imprinted gene on proximal chromosome 7 encodes for a zinc finger protein.
    Nat Genet. 1996 Feb;12(2):186-90 PMID: 8563758
  8. Allele-specific in situ hybridization (ASISH) analysis: a novel technique which resolves differential allelic usage of H19 within the same cell lineage during human placental development.
    Development. 1996 Mar;122(3):839-47 PMID: 8631262
  9. Selective maternal-allele loss in human lung cancers of the maternally expressed p57KIP2 gene at 11p15.5.
    Oncogene. 1996 Mar 21;12(6):1365-8 PMID: 8649840
  10. Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient.
    Hum Mol Genet. 1996 Apr;5(4):517-24 PMID: 8845846
  11. DNA methylation patterns in human tissues of uniparental origin using a zinc-finger gene (ZNF127) from the Angelman/Prader-Willi region.
    Am J Med Genet. 1996 Jan 11;61(2):140-6 PMID: 8669440
  12. Genomic imprinting of human p57KIP2 and its reduced expression in Wilms' tumors.
    Hum Mol Genet. 1996 Jun;5(6):783-8 PMID: 8776593
  13. Identification of Grf1 on mouse chromosome 9 as an imprinted gene by RLGS-M.
    Nat Genet. 1996 Sep;14(1):106-9 PMID: 8782830
  14. Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN gene.
    Nat Genet. 1996 Oct;14(2):163-70 PMID: 8841186
  15. An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome.
    Nat Genet. 1996 Oct;14(2):171-3 PMID: 8841187
  16. Imprinting mutation in the Beckwith-Wiedemann syndrome leads to biallelic IGF2 expression through an H19-independent pathway.
    Hum Mol Genet. 1996 Dec;5(12):2027-32 PMID: 8968759
  17. Reduced expression of the cyclin-dependent kinase inhibitor gene p57KIP2 in Wilms' tumor.
    Cancer Res. 1996 Dec 15;56(24):5723-7 PMID: 8971182
  18. Mice devoid of gamma-aminobutyrate type A receptor beta3 subunit have epilepsy, cleft palate, and hypersensitive behavior.
    Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4143-8 PMID: 9108119
  19. Expression of genes from the human active and inactive X chromosomes.
    Am J Hum Genet. 1997 Jun;60(6):1333-43 PMID: 9199554
  20. Imprinting in clusters: lessons from Beckwith-Wiedemann syndrome.
    Trends Genet. 1997 Aug;13(8):330-4 PMID: 9260520
  21. A 1-Mb physical map and PAC contig of the imprinted domain in 11p15.5 that contains TAPA1 and the BWSCR1/WT2 region.
    Genomics. 1997 Aug 1;43(3):366-75 PMID: 9268640
  22. Evidence for uniparental, paternal expression of the human GABAA receptor subunit genes, using microcell-mediated chromosome transfer.
    Hum Mol Genet. 1997 Nov;6(12):2127-33 PMID: 9328477
  23. The human necdin gene, NDN, is maternally imprinted and located in the Prader-Willi syndrome chromosomal region.
    Nat Genet. 1997 Nov;17(3):357-61 PMID: 9354807
  24. The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse.
    Hum Mol Genet. 1997 Oct;6(11):1873-8 PMID: 9302265
  25. CD81 on B cells promotes interleukin 4 secretion and antibody production during T helper type 2 immune responses.
    Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2458-62 PMID: 9482907
  26. IMPT1, an imprinted gene similar to polyspecific transporter and multi-drug resistance genes.
    Hum Mol Genet. 1998 Apr;7(4):597-608 PMID: 9499412
  27. Human X-Linked genes regionally mapped utilizing X-autosome translocations and somatic cell hybrids.
    Proc Natl Acad Sci U S A. 1975 Jun;72(6):2125-9 PMID: 1056018
  28. Human gene mapping using an X/autosome translocation.
    Somatic Cell Genet. 1976 Mar;2(2):125-40 PMID: 69325
  29. Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation.
    Science. 1981 Jan 23;211(4480):393-6 PMID: 6164095
  30. Gene on short arm of human X chromosome complements murine tsA1S9 DNA synthesis mutation.
    Somat Cell Mol Genet. 1989 Mar;15(2):173-8 PMID: 2928842
  31. Differential imprinting and expression of maternal and paternal genomes.
    Annu Rev Genet. 1988;22:127-46 PMID: 3071246
  32. Divergently transcribed overlapping genes expressed in liver and kidney and located in the 11p15.5 imprinted domain.
    Genomics. 1998 Apr 1;49(1):38-51 PMID: 9570947
  33. Multiple mechanisms regulate imprinting of the mouse distal chromosome 7 gene cluster.
    Mol Cell Biol. 1998 Jun;18(6):3466-74 PMID: 9584186
  34. Mutation analysis of UBE3A in Angelman syndrome patients.
    Am J Hum Genet. 1998 Jun;62(6):1353-60 PMID: 9585605
  35. Imprinting in Prader-Willi and Angelman syndromes.
    Trends Genet. 1998 May;14(5):194-200 PMID: 9613204
  36. Autosomal and X-chromosome imprinting.
    Dev Suppl. 1990;:63-72 PMID: 2090432
  37. The human ribonuclease/angiogenin inhibitor is encoded by a gene mapped to chromosome 11p15.5, within 90 kb of the HRAS protooncogene.
    Cytogenet Cell Genet. 1992;59(4):264-7 PMID: 1544320
  38. Equivalent expression of paternally and maternally inherited WT1 alleles in normal fetal tissue and Wilms' tumours.
    Oncogene. 1992 Apr;7(4):635-41 PMID: 1314367
  39. Isolation of monochromosomal hybrids following fusion of human diploid fibroblast-derived microcells with mouse A9 cells.
    Cytogenet Cell Genet. 1992;60(1):79-80 PMID: 1582264
  40. Elevated sister chromatid exchange phenotype of Bloom syndrome cells is complemented by human chromosome 15.
    Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):7968-72 PMID: 1518822
  41. Expression of necdin, an embryonal carcinoma-derived nuclear protein, in developing mouse brain.
    Brain Res Dev Brain Res. 1992 Aug 21;68(2):265-74 PMID: 1394972
  42. Evaluation of potential models for imprinted and nonimprinted components of human chromosome 15q11-q13 syndromes by fine-structure homology mapping in the mouse.
    Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):2050-4 PMID: 8095339
  43. Monoallelic expression of the human H19 gene.
    Nat Genet. 1992 Apr;1(1):40-4 PMID: 1363808
  44. Parental genomic imprinting of the human IGF2 gene.
    Nat Genet. 1993 May;4(1):98-101 PMID: 8099843
  45. The inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic marker for gene expression.
    Cell. 1993 Jul 30;74(2):281-9 PMID: 8343956
  46. Oppositely imprinted genes H19 and insulin-like growth factor 2 are coexpressed in human androgenetic trophoblast.
    Am J Hum Genet. 1993 Nov;53(5):1096-102 PMID: 7692725
  47. The insulin-like growth factor type-2 receptor gene is imprinted in the mouse but not in humans.
    Nat Genet. 1993 Sep;5(1):74-8 PMID: 8220428
  48. Characterization of a methylation imprint in the Prader-Willi syndrome chromosome region.
    Hum Mol Genet. 1993 Dec;2(12):1995-9 PMID: 8111366
  49. Functional imprinting and epigenetic modification of the human SNRPN gene.
    Hum Mol Genet. 1993 Dec;2(12):2001-5 PMID: 8111367
  50. Identification of an imprinted U2af binding protein related sequence on mouse chromosome 11 using the RLGS method.
    Nat Genet. 1994 Jan;6(1):33-40 PMID: 8136831
  51. Phenotypic consequences of deletion of the gamma 3, alpha 5, or beta 3 subunit of the type A gamma-aminobutyric acid receptor in mice.
    Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2815-8 PMID: 8146195
  52. GABAA receptor beta 3 subunit gene is possibly paternally imprinted in humans.
    Am J Med Genet. 1994 Feb 15;49(4):452-3 PMID: 8160743
  53. Single nucleotide dimorphism in the transcribed region of the SNRPN gene at 15q12.
    Hum Mol Genet. 1994 Feb;3(2):379 PMID: 7911699
  54. Mosaic and polymorphic imprinting of the WT1 gene in humans.
    Nat Genet. 1994 Mar;6(3):305-9 PMID: 8012395
  55. Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region.
    Nat Genet. 1994 Sep;8(1):52-8 PMID: 7987392
  56. Established epigenetic modifications determine the expression of developmentally regulated globin genes in somatic cell hybrids.
    Mol Cell Biol. 1995 Aug;15(8):3969-78 PMID: 7623793
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.95.25.14857
Published
1998-12-08
Pages
14857-62
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24540
Subset
IM
Grants
NCI NIH HHS · CA63333 · United States
NIGMS NIH HHS · T32 GM008613 · United States
NICHD NIH HHS · HD31491 · United States
NIGMS NIH HHS · GM08613 · United States
NICHD NIH HHS · R01 HD031491 · United States
External Links
PubMed source DOI: 10.1073/pnas.95.25.14857 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2