The 3′ portion of the mouse <i>H19</i> Imprinting-Control Region is required for proper tissue-specific expression of the <i>Igf2 </i>gene

Vol. 113, No. 1-4, 2006

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Imprinted Genes/Domains

The 3' portion of the mouse H19 Imprinting-Control Region is required for proper tissue-specific expression of the Igf2 gene
H. Hagège^a, R. Nasser^a, M. Weber^a, L. Milligan^a, N. Aptel^a, C. Jacquet^a, R.A. Drewell^b, L. Dandolo^c, M.A. Surani^d, G. Cathala^a, T. Forné^a

^aInstitut de Génétique Moléculaire de Montpellier, Montpellier (France);
^bBiology Department, University of Nevada, Reno, NV (USA);

Address of Corresponding Author

Cytogenet Genome Res 2006;113:230-237 (DOI: 10.1159/000090837)

Abstract.

Genomic imprinting at the H19/Igf2 locus is governed by a cis-acting Imprinting-Control Region (ICR), located 2 kb upstream of the H19 gene. This region possesses an insulator function which is activated on the unmethylated maternal allele through the binding of the CTCF factor. It has been previously reported that paternal transmission of the H19^SilK deletion, which removes the 3' portion of H19 ICR, leads to the loss of H19 imprinting. Here we show that, in the liver, this reactivation of the paternal H19 gene is concomitant to a dramatic decrease in Igf2 mRNA levels. This deletion alters higher-order chromatin architecture, Igf2 promoter usage and tissue-specific expression. Therefore, when methylated, the 3' portion of the H19 ICR is a bi-functional regulatory element involved not only in H19 imprinting but also in 'formatting' the higher-order chromatin structure for proper tissue-specific expression of both H19 and Igf2 genes.

Author Contacts

Request reprints from Drs. Guy Cathala or Thierry Forné
Institut de Génétique Moléculaire, CNRS UMR 5535
1919 route de Mende, F-34293 Montpellier cedex 5 (France)
telephone: +33-467-613-684; fax: +33-467-040-231
e-mail: forne@igmm.cnrs.fr
Present address of M.W.: Friedrich Miescher Institute for Biomedical Research Novartis Research Foundation Maulbeerstrasse 66, CH-4058, Basel (Switzerland)
Present address of L.M.: Wellcome Trust Centre for Biology, ICMB University of Edinburgh, King's Buildings, Edinburgh EH9 3JR (UK)

Article Information

Supported by the Association pour la Recherche contre le Cancer (ARC contract No. 3279), the French Ministry of Research and Technology (GIS 'Longevité', contract No. GISLO401) and the Fond National de la Science (ACI jeune chercheur given to T.F.). L.M. was supported by a fellowship from the Fondation pour la recherche médicale.

Manuscript received: 29 June 2005
Accepted in revised form for publication by F. Ishino,: 15 September 2005.
Number of Print Pages : 8
Number of Figures : 5, Number of Tables : 1, Number of References : 27

Medline Abstract (ID 16575185)

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