H3K4 tri-methylation provides an epigenetic signature of active enhancers

Authors

  • Aleksandra Pekowska,

    1. Centre d'Immunologie de Marseille-Luminy (CIML), Parc Scientifique de Luminy, Case 906, Marseille, France
    2. CNRS, UMR6102, Marseille, France
    3. Inserm, U631, Marseille, France
    4. Université de la Méditerranée, Marseille, France
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    • These authors contributed equally to this work
    • Present address: European Molecular Biology Laboratory, Heidelberg, Germany
  • Touati Benoukraf,

    1. Centre d'Immunologie de Marseille-Luminy (CIML), Parc Scientifique de Luminy, Case 906, Marseille, France
    2. CNRS, UMR6102, Marseille, France
    3. Inserm, U631, Marseille, France
    4. Université de la Méditerranée, Marseille, France
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    • These authors contributed equally to this work
    • Present address: Cancer Science Institute of Singapore, National University of Singapore, Singapore
  • Joaquin Zacarias-Cabeza,

    1. Centre d'Immunologie de Marseille-Luminy (CIML), Parc Scientifique de Luminy, Case 906, Marseille, France
    2. CNRS, UMR6102, Marseille, France
    3. Inserm, U631, Marseille, France
    4. Université de la Méditerranée, Marseille, France
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    • These authors contributed equally to this work
  • Mohamed Belhocine,

    1. Centre d'Immunologie de Marseille-Luminy (CIML), Parc Scientifique de Luminy, Case 906, Marseille, France
    2. CNRS, UMR6102, Marseille, France
    3. Inserm, U631, Marseille, France
    4. Université de la Méditerranée, Marseille, France
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  • Frederic Koch,

    1. Centre d'Immunologie de Marseille-Luminy (CIML), Parc Scientifique de Luminy, Case 906, Marseille, France
    2. CNRS, UMR6102, Marseille, France
    3. Inserm, U631, Marseille, France
    4. Université de la Méditerranée, Marseille, France
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  • Hélène Holota,

    1. Université de la Méditerranée, Marseille, France
    2. Inserm, U928, TAGC, Marseille, France
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  • Jean Imbert,

    1. Université de la Méditerranée, Marseille, France
    2. Inserm, U928, TAGC, Marseille, France
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  • Jean-Christophe Andrau,

    1. Centre d'Immunologie de Marseille-Luminy (CIML), Parc Scientifique de Luminy, Case 906, Marseille, France
    2. CNRS, UMR6102, Marseille, France
    3. Inserm, U631, Marseille, France
    4. Université de la Méditerranée, Marseille, France
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  • Pierre Ferrier,

    Corresponding author
    1. Centre d'Immunologie de Marseille-Luminy (CIML), Parc Scientifique de Luminy, Case 906, Marseille, France
    2. CNRS, UMR6102, Marseille, France
    3. Inserm, U631, Marseille, France
    4. Université de la Méditerranée, Marseille, France
    • Corresponding authors: Centre d'Immunologie de Marseille-Luminy (CIML), Parc Scientifique de Luminy, Case 906, Marseille 13009, France. Tel.: +33 49 126 9435; Fax: +33 49 126 9430; E-mail: ferrier@ciml.univ-mrs.fr or Tel.: +33 49 126 9443; Fax: +33 49 126 9430; E-mail: spicuglia@ciml.univ-mrs.fr

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  • Salvatore Spicuglia

    Corresponding author
    1. Centre d'Immunologie de Marseille-Luminy (CIML), Parc Scientifique de Luminy, Case 906, Marseille, France
    2. CNRS, UMR6102, Marseille, France
    3. Inserm, U631, Marseille, France
    4. Université de la Méditerranée, Marseille, France
    • Corresponding authors: Centre d'Immunologie de Marseille-Luminy (CIML), Parc Scientifique de Luminy, Case 906, Marseille 13009, France. Tel.: +33 49 126 9435; Fax: +33 49 126 9430; E-mail: ferrier@ciml.univ-mrs.fr or Tel.: +33 49 126 9443; Fax: +33 49 126 9430; E-mail: spicuglia@ciml.univ-mrs.fr

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Abstract

Combinations of post-translational histone modifications shape the chromatin landscape during cell development in eukaryotes. However, little is known about the modifications exactly delineating functionally engaged regulatory elements. For example, although histone H3 lysine 4 mono-methylation (H3K4me1) indicates the presence of transcriptional gene enhancers, it does not provide clearcut information about their actual position and stage-specific activity. Histone marks were, therefore, studied here at genomic loci differentially expressed in early stages of T-lymphocyte development. The concomitant presence of the three H3K4 methylation states (H3K4me1/2/3) was found to clearly reflect the activity of bona fide T-cell gene enhancers. Globally, gain or loss of H3K4me2/3 at distal genomic regions correlated with, respectively, the induction or the repression of associated genes during T-cell development. In the Tcrb gene enhancer, the H3K4me3-to-H3K4me1 ratio decreases with the enhancer's strength. Lastly, enhancer association of RNA-polymerase II (Pol II) correlated with the presence of H3K4me3 and Pol II accumulation resulted in local increase of H3K4me3. Our results suggest the existence of functional links between Pol II occupancy, H3K4me3 enrichment and enhancer activity.

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