Biology of Repetitive Sequences

 Jérôme DEJARDIN

 IGH - UMR 9004

 141, rue de la Cardonille, 34396 Montpellier

Phone: +33 4 34 35 99 45

Email: jerome.dejardin@igh.cnrs.fr

 Website

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).

Keywords:

Main publications:

• Telomere chromatin establishment and its maintenance during mammalian development. Tardat M, Déjardin J. Chromosoma. 2018 Mar;127(1):3-18.
• Histone H4K20 tri-methylation at late-firing origins ensures timely heterochromatin replication. Brustel J, Kirstein N, Izard F, Grimaud C, Prorok P, Cayrou C, Schotta G, Abdelsamie AF, Déjardin J, Méchali M, Baldacci G, Sardet C, Cadoret JC, Schepers A, Julien E. 2017 - EMBO J., 36(18):2726-2741.
• The cell proliferation antigen Ki-67 organises heterochromatin. Sobecki M, Mrouj K, Camasses A, Parisis N, Nicolas E, Llères D, Gerbe F, Prieto S, Krasinska L, David A, Eguren M, Birling MC, Urbach S, Hem S, Déjardin J, Malumbres M, Jay P, Dulic V, Lafontaine DL, Feil RP, Fisher D 2016 - Elife, 5, e13722.
• Nuclear-Receptor-Mediated Telomere Insertion Leads to Genome Instability in ALT Cancer. Marzec, P., Armenise, C., Perot, G., Roumelioti, F.M., Basyuk, E., Gagos, S., Chibon, F., Dejardin, J. 2015 - CELL, 160, 5, 913-927.
• End-targeting proteomics of isolated chromatin segments of a mammalian ribosomal RNA gene promoter. Ide, S., Dejardin, J. 2015 - Nat. Commun., 6, 6674.
• Switching between Epigenetic States at Pericentromeric Heterochromatin. Dejardin, J. 2015 - Trends Genet, 31, 11, 661-672.
• Redundant Mechanisms to Form Silent Chromatin at Pericentromeric Regions Rely on BEND3 and DNA Methylation. Saksouk N, Barth TK, Ziegler-Birling C, Olova N, Nowak A, Rey E, Mateos-Langerak J, Urbach S, Reik W, Torres-Padilla ME, Imhof A, Déjardin J. 2014 - Mol Cell, 56(4):580-94.