Human Molecular Genetics, Vol 6, 1543-1548, Copyright © 1997 by Oxford University Press
JA Joyce, WK Lam, DJ Catchpoole, P Jenks, W Reik, ER Maher and PN Schofield
Genomic imprinting is a novel form of control of gene expression in which
the transcription of each allele of an imprinted gene is dependent on the
sex of the gamete from which it was derived; to date > 15 genes have
been demonstrated to show imprinting. The maintenance of a normal
imprinting pattern in many loci has been shown to be essential for normal
development and adult life. Many tumours, and some developmental disorders,
exhibit loss of imprinting (LOI) in key genes such as insulin-like growth
factor 2 (IGF2) which often results in hyperplasia and is associated with
cancer. The mechanism by which the genomic imprint is first established,
then maintained, is not understood. However, in the case of IGF2, the
expression of a neighbouring gene, H19, has been suggested to influence its
transcription by competition for a common enhancer, thereby generating a
mutually exclusive and allele-specific pattern of gene expression.
Associated changes in CpG methylation in discrete areas of both genes have
been implicated in maintenance of the imprint. We have examined the
allele-specific expression of IGF2 and H19 in fibroblasts derived from
patients with sporadic Beckwith-Wiedemann syndrome (BWS), a fetal
overgrowth syndrome associated with an imprinted locus on 11p15.5. We
report that the majority of karyotypically normal patients show LOI of IGF2
with biallelic expression. In a proportion of these patients, loss of IGF2
imprinting was associated with complete suppression of H19 expression, as
predicted by the enhancer competition model. However, in a significant
number of cases, IGF2 showed biallelic expression even though H19
expression and methylation status were normal. This indicates that there
must be an alternative H19-independent pathway by which allele-specific
IGF2 expression is established or maintained.
ARTICLES
Imprinting of IGF2 and H19: lack of reciprocity in sporadic Beckwith- Wiedemann syndrome
Department of Anatomy, University of Cambridge, UK.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F. Cerrato, A. Sparago, G. Verde, A. De Crescenzo, V. Citro, M. V. Cubellis, M. M. Rinaldi, L. Boccuto, G. Neri, C. Magnani, et al. Different mechanisms cause imprinting defects at the IGF2/H19 locus in Beckwith-Wiedemann syndrome and Wilms' tumour Hum. Mol. Genet., May 15, 2008; 17(10): 1427 - 1435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Algar, L. St. Heaps, A. Darmanian, V. Dagar, D. Prawitt, G. B. Peters, and F. Collins Paternally Inherited Submicroscopic Duplication at 11p15.5 Implicates Insulin-like Growth Factor II in Overgrowth and Wilms' Tumorigenesis Cancer Res., March 1, 2007; 67(5): 2360 - 2365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Monk, R. Sanches, P. Arnaud, S. Apostolidou, F.A. Hills, S. Abu-Amero, A. Murrell, H. Friess, W. Reik, P. Stanier, et al. Imprinting of IGF2 P0 transcript and novel alternatively spliced INS-IGF2 isoforms show differences between mouse and human Hum. Mol. Genet., April 15, 2006; 15(8): 1259 - 1269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Cerrato, A. Sparago, I. D. Matteo, X. Zou, W. Dean, H. Sasaki, P. Smith, R. Genesio, M. Bruggemann, W. Reik, et al. The two-domain hypothesis in Beckwith-Wiedemann syndrome: autonomous imprinting of the telomeric domain of the distal chromosome 7 cluster Hum. Mol. Genet., February 15, 2005; 14(4): 503 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Murrell, S. Heeson, W. N. Cooper, E. Douglas, S. Apostolidou, G. E. Moore, E. R. Maher, and W. Reik An association between variants in the IGF2 gene and Beckwith-Wiedemann syndrome: interaction between genotype and epigenotype Hum. Mol. Genet., January 15, 2004; 13(2): 247 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. S. Mitchell, A. T. Hattersley, B. Knight, T. Turner, B. S. Metcalf, L. D. Voss, D. Davies, A. McCarthy, T. J. Wilkin, G. D. Smith, et al. Lack of Support for a Role of the Insulin Gene Variable Number of Tandem Repeats Minisatellite (INS-VNTR) Locus in Fetal Growth or Type 2 Diabetes-Related Intermediate Traits in United Kingdom Populations J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 310 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Diaz-Meyer, C D Day, K Khatod, E R Maher, W Cooper, W Reik, C Junien, G Graham, E Algar, V M Der Kaloustian, et al. Silencing of CDKN1C (p57KIP2) is associated with hypomethylation at KvDMR1 in Beckwith-Wiedemann syndrome J. Med. Genet., November 1, 2003; 40(11): 797 - 801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Du, L. G. Beatty, W. Zhou, J. Lew, C. Schoenherr, R. Weksberg, and P. D. Sadowski Insulator and silencer sequences in the imprinted region of human chromosome 11p15.5 Hum. Mol. Genet., August 1, 2003; 12(15): 1927 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Weksberg, A. C. Smith, J. Squire, and P. Sadowski Beckwith-Wiedemann syndrome demonstrates a role for epigenetic control of normal development Hum. Mol. Genet., April 2, 2003; 12(90001): R61 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kaplan, K. Luettich, A. Heguy, N. R. Hackett, B.-G. Harvey, and R. G. Crystal Monoallelic Up-Regulation of the Imprinted H19 Gene in Airway Epithelium of Phenotypically Normal Cigarette Smokers Cancer Res., April 1, 2003; 63(7): 1475 - 1482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Weksberg, C. Shuman, O. Caluseriu, A. C. Smith, Y.-L. Fei, J. Nishikawa, T. L. Stockley, L. Best, D. Chitayat, A. Olney, et al. Discordant KCNQ1OT1 imprinting in sets of monozygotic twins discordant for Beckwith-Wiedemann syndrome Hum. Mol. Genet., May 16, 2002; 11(11): 1317 - 1325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Weksberg, J. Nishikawa, O. Caluseriu, Y.-L. Fei, C. Shuman, C. Wei, L. Steele, J. Cameron, A. Smith, I. Ambus, et al. Tumor development in the Beckwith-Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1 Hum. Mol. Genet., December 1, 2001; 10(26): 2989 - 3000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. John, J. F. -X. Ainscough, S. C. Barton, and M. A. Surani Distant cis-elements regulate imprinted expression of the mouse p57 Kip2 (Cdkn1c) gene: implications for the human disorder, Beckwith-Wiedemann syndrome Hum. Mol. Genet., July 1, 2001; 10(15): 1601 - 1609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F Costello and C. Plass Methylation matters J. Med. Genet., May 1, 2001; 38(5): 285 - 303. [Abstract] [Full Text]
|
|
|
|
|
|
J. Bliek, S. M. Maas, J. M. Ruijter, R. C.M. Hennekam, M. Alders, A. Westerveld, and M. M.A.M. Mannens Increased tumour risk for BWS patients correlates with aberrant H19 and not KCNQ1OT1 methylation: occurrence of KCNQ1OT1 hypomethylation in familial cases of BWS Hum. Mol. Genet., March 1, 2001; 10(5): 467 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R Engel, A. Smallwood, A. Harper, M. J Higgins, M. Oshimura, W. Reik, P. N Schofield, and E. R Maher Epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome J. Med. Genet., December 1, 2000; 37(12): 921 - 926. [Abstract] [Full Text]
|
|
|
|
|
|
S.-i. Horike, K. Mitsuya, M. Meguro, N. Kotobuki, A. Kashiwagi, T. Notsu, T. C. Schulz, Y. Shirayoshi, and M. Oshimura Targeted disruption of the human LIT1 locus defines a putative imprinting control element playing an essential role in Beckwith-Wiedemann syndrome Hum. Mol. Genet., September 1, 2000; 9(14): 2075 - 2083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Muller, D. van den Boom, D. Zirkel, H. Koster, F. Berthold, M. Schwab, M. Westphal, and W. Zumkeller Retention of imprinting of the human apoptosis-related gene TSSC3 in human brain tumors Hum. Mol. Genet., March 22, 2000; 9(5): 757 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Juan, C. Crain, and C. Wilson Evidence for evolutionarily conserved secondary structure in the H19 tumor suppressor RNA Nucleic Acids Res., March 1, 2000; 28(5): 1221 - 1227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. CATCHPOOLE, A. V SMALLWOOD, J. A JOYCE, A. MURRELL, W. LAM, T. TANG, D. MUNROE, W. REIK, P. N SCHOFIELD, and E. R MAHER Mutation analysis of H19 and NAP1L4 (hNAP2) candidate genes and IGF2 DMR2 in Beckwith-Wiedemann syndrome J. Med. Genet., March 1, 2000; 37(3): 212 - 215. [Full Text]
|
|
|
|
|
|
A. B. Hassan and J. A. Howell Insulin-like Growth Factor II Supply Modifies Growth of Intestinal Adenoma in ApcMin/+ Mice Cancer Res., February 1, 2000; 60(4): 1070 - 1076. [Abstract] [Full Text]
|
|
|
|
 |
|
 C.-L. Chen, S.-M. Ip, D. Cheng, L.-C. Wong, and H. Y. S. Ngan Loss of Imprinting of the IGF-II and H19 Genes in Epithelial Ovarian Cancer Clin. Cancer Res., February 1, 2000; 6(2): 474 - 479. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Ainscough, R. John, S. Barton, and M. Surani A skeletal muscle-specific mouse Igf2 repressor lies 40 kb downstream of the gene Development, January 9, 2000; 127(18): 3923 - 3930. [Abstract] [PDF]
|
|
|
|
 |
|
 N. J. Smilinich, C. D. Day, G. V. Fitzpatrick, G. M. Caldwell, A. C. Lossie, P. R. Cooper, A. C. Smallwood, J. A. Joyce, P. N. Schofield, W. Reik, et al. A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Wiedemann syndrome PNAS, July 6, 1999; 96(14): 8064 - 8069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mitsuya, M. Meguro, M. P. Lee, M. Katoh, T. C. Schulz, H. Kugoh, M. A. Yoshida, N. Niikawa, A. P. Feinberg, and M. Oshimura LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids Hum. Mol. Genet., July 1, 1999; 8(7): 1209 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. W K Lam, I. Hatada, S. Ohishi, T. Mukai, J. A Joyce, T. R P Cole, D. Donnai, W. Reik, P. N Schofield, and E. R Maher Analysis of germline CDKN1C (p57KIP2) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype correlation J. Med. Genet., July 1, 1999; 36(7): 518 - 523. [Abstract] [Full Text]
|
|
|
|
|
|
M. P. Lee, M. R. DeBaun, K. Mitsuya, H. L. Galonek, S. Brandenburg, M. Oshimura, and A. P. Feinberg Loss of imprinting of a paternally expressed transcript, with antisense orientation to KVLQT1, occurs frequently in Beckwith-Wiedemann syndrome and is independent of insulin-like growth factor II imprinting PNAS, April 27, 1999; 96(9): 5203 - 5208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Falls, D. J. Pulford, A. A. Wylie, and R. L. Jirtle Genomic Imprinting: Implications for Human Disease Am. J. Pathol., March 1, 1999; 154(3): 635 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hahn, L. Wojnowski, K. Specht, R. Kappler, J. Calzada-Wack, D. Potter, A. Zimmer, U. Muller, E. Samson, L. Quintanilla-Martinez, et al. Patched Target Igf2 Is Indispensable for the Formation of Medulloblastoma and Rhabdomyosarcoma J. Biol. Chem., September 8, 2000; 275(37): 28341 - 28344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Grandjean, J. Smith, P. N. Schofield, and A. C. Ferguson-Smith Increased IGF-II protein affects p57kip2 expression in vivo and in vitro: Implications for Beckwith-Wiedemann syndrome PNAS, May 9, 2000; 97(10): 5279 - 5284. [Abstract] [Full Text] [PDF]
|
|