Biologie des Séquences Répétées

  • Chromatin can be viewed as a highly complex mixture of proteins and nucleic acids that orchestrate DNA-based processes in the eukaryotic genome. Most of the mammalian genome is assembled into heterochromatin, a ‘closed’ structure imposed by several enzymatic activities. Such activities act on histones and the DNA itself to impinge on transcription, replication or repair.
    Most of the heterochromatic fraction of the genome can be found at critical loci. These include telomeres, repetitive sequences around centromeres and a portion (about half) of the gene units encoding ribosomal RNAs. Defects in the regulation of these loci have therefore disastrous consequences on cell identity and can lead to developmental problems, cancer, premature aging or immune deficiencies. How precisely heterochromatic enzymes affect the composition of target loci has remained elusive and research in our laboratory primarily focuses on this question.
    To understand how heterochromatin acts at the molecular level, we are looking at the effect of abrogating important heterochromatic activities, such as histone and/or DNA methyl-transferases, on the overall composition of key heterochromatic loci (telomeres, pericentromeres and rDNA).

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    Membres

    Jérôme Dejardin
    Dejardin Jérôme
    Mathieu Tardat
    Tardat Mathieu
    Sihem Zitouni
    Zitouni Sihem
    Sandrine Sauzet
    Sauzet Sandrine
    Assia Bouhayane
    Bouhayane Assia
    Lucas Ducrot
    Ducrot Lucas
    Bariaa Hamade
    Hamade Bariaa
    Varinia Garcia molinero
    Garcia molinero Varinia
    Amandine Barral
    Barral Amandine

    Publications

    Telomeric Chromatin and TERRA.

    Barral A, Déjardin J

    2020 - J Mol Biol

    Demander l'article complet32151584

    Purification and enrichment of specific chromatin loci.

    Gauchier M, van Mierlo G, Vermeulen M, Déjardin J

    2020 - Nat Methods, 17(4):380-389

    Demander l'article complet32152500

    Locus-specific chromatin isolation.

    Vermeulen M, Déjardin J

    2020 - Nat Rev Mol Cell Biol, 21(5):249-250

    Demander l'article complet31996790

    Remodeling and destabilization of chromosome 1 pericentromeric heterochromatin by SSX proteins.

    Traynor S, Møllegaard NE, Jørgensen MG, Brückmann NH, Pedersen CB, Terp MG, Johansen S, Dejardin J, Ditzel HJ, Gjerstorff MF

    2019 - Nucleic Acids Res, 47(13):6668-6684

    Demander l'article complet31114908
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    Publications de l'équipe

  • ERC consolidator grant 2016: ‘METACHROM’

    logo ercMetastable epialleles are alleles that are variably expressed in genetically identical individuals. These epialleles are established during early development by epigenetic modifications in a process influenced by stress and the environment. The epiallele’s state can subsequently be maintained throughout development and adult life. Studying the mechanisms underlying establishment and maintenance of chromatin states is critical to understanding how the environment can shape the epigenome and how it can impact on diseases and aging. Most mouse metastable epialleles result from a nearby insertion of an endogenous retrovirus, which induces position effect variegation. In mouse embryonic stem cells, these elements are silenced by the histone methyl-transferase SETDB1 which imparts heterochromatin features by tri-methylating histone H3 on lysine 9. In the same cells, telomeric H3K9me3 is also installed by SETDB1 but surprisingly, we found that H3K9me3 correlates with transcriptional activity at telomeres. I hypothesize here that metastable chromatin states are controlled by H3K9me3 and associated factors, which are targeted to defined positions that can either instruct silencing, or support active expression. To understand how metastable chromatin states are regulated, we will first use a locus-specific chromatin proteomics approach to identify H3K9me3-dependent factors in the contexts of transcription or repression. Next, both pathways will be reconstituted by tethering those factors at specific positions on model genes, and maintenance of these states will be analyzed. Finally, to obtain a comprehensive picture of the metastable states establishment and maintenance, we will map heterochromatin factors genome-wide, in response to distinct stimuli in mESCs. This proposal will deepen our understanding of the mechanisms by which mammals use gene regulation to adapt to environmental conditions.

    Telomeric Chromatin and TERRA.

    Barral A, Déjardin J

    2020 - J Mol Biol

    Demander l'article complet32151584

    Purification and enrichment of specific chromatin loci.

    Gauchier M, van Mierlo G, Vermeulen M, Déjardin J

    2020 - Nat Methods, 17(4):380-389

    Demander l'article complet32152500

    Locus-specific chromatin isolation.

    Vermeulen M, Déjardin J

    2020 - Nat Rev Mol Cell Biol, 21(5):249-250

    Demander l'article complet31996790

    Remodeling and destabilization of chromosome 1 pericentromeric heterochromatin by SSX proteins.

    Traynor S, Møllegaard NE, Jørgensen MG, Brückmann NH, Pedersen CB, Terp MG, Johansen S, Dejardin J, Ditzel HJ, Gjerstorff MF

    2019 - Nucleic Acids Res, 47(13):6668-6684

    Demander l'article complet31114908