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  • The EMBO Journal (2008) 27, 2523 - 2532
  • doi:10.1038/emboj.2008.142

Published online: 24 July 2008

A mono-allelic bivalent chromatin domain controls tissue-specific imprinting at Grb10

Lionel A Sanz1, Stormy Chamberlain2,a, Jean-Charles Sabourin3,a, Amandine Henckel1, Terry Magnuson2, Jean-Philippe Hugnot3, Robert Feil1 and Philippe Arnaud1

  1. Institute of Molecular Genetics, CNRS UMR-5535 and University of Montpellier II, Montpellier, France
  2. Department of Genetics, Carolina Center for the Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  3. INSERM U583, Physiopathologie et Thérapie des Déficits Sensoriels et Moteurs, Institut des Neurosciences de Montpellier, Hôpital St Eloi, Montpellier, France

Correspondence to:

Philippe Arnaud, Institute of Molecular Genetics, CNRS UMR-5535 and University of Montpellier II, 1919 route de Mende, Montpellier 34293, France. Tel.: +33 4 6761 3661; Fax: +33 4 6704 0231; E-mail: philippe.arnaud@igmm.cnrs.fr

Robert Feil, Institute of Molecular Genetics, CNRS UMR-5535 and University of Montpellier II, 1919 route de Mende, Montpellier 34293, France. Tel.: +33 4 6761 3661; Fax: +33 4 6704 0231; E-mail: robert.feil@igmm.cnrs.fr

aThese authors contributed equally to this work

Received 4 March 2008; Accepted 27 June 2008

Genomic imprinting is a developmental mechanism that mediates parent-of-origin-specific expression in a subset of genes. How the tissue specificity of imprinted gene expression is controlled remains poorly understood. As a model to address this question, we studied Grb10, a gene that displays brain-specific expression from the paternal chromosome. Here, we show in the mouse that the paternal promoter region is marked by allelic bivalent chromatin enriched in both H3K4me2 and H3K27me3, from early embryonic stages onwards. This is maintained in all somatic tissues, but brain. The bivalent domain is resolved upon neural commitment, during the developmental window in which paternal expression is activated. Our data indicate that bivalent chromatin, in combination with neuronal factors, controls the paternal expression of Grb10 in brain. This finding highlights a novel mechanism to control tissue-specific imprinting.

  • Keywords:

    • bivalent chromatin,
    • Eed,
    • Grb10,
    • imprinting,
    • tissue-specific imprinting