Dynamic methylation of histone H3K18 in differentiating Theileria parasites

Autor: Kevin Cheeseman, Guillaume Jannot, Nelly Lourenco, Marie Villares, Jeremy BERTHELET, Teresa Calegari-Silva, Juliette Hamroune, Franck Letourneur, Fernando Rodrigues-Lima, Jonathan Weitzman
Přispěvatelé: Manquant, Mathieu, Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Cochin (IC UM3 (UMR 8104 / U1016))
Rok vydání: 2020
Předmět:
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021)
Nature Communications
Nature Communications, 2021, 12 (1), ⟨10.1038/s41467-021-23477-2⟩
ISSN: 2041-1723
Popis: Lysine methylation on histone tails impacts genome regulation and cell fate determination in many developmental processes. Apicomplexa intracellular parasites cause major diseases and they have developed complex life cycles with fine-tuned differentiation events. Yet, apicomplexa genomes have few transcription factors and little is known about their epigenetic control systems. Tick-borne Theileria apicomplexa species have relatively small, compact genomes and a remarkable ability to transform leucocytes in their bovine hosts. Here we report enriched H3 lysine 18 monomethylation (H3K18me1) on the gene bodies of repressed genes in Theileria macroschizonts. Differentiation to merozoites (merogony) leads to decreased H3K18me1 in parasite nuclei. Pharmacological manipulation of H3K18 acetylation or methylation impacted parasite differentiation and expression of stage-specific genes. Finally, we identify a parasite SET-domain methyltransferase (TaSETup1) that can methylate H3K18 and represses gene expression. Thus, H3K18me1 emerges as an important epigenetic mark which controls gene expression and stage differentiation in Theileria parasites.
Post-translational modifications (PTM) of histones are important for epigenetic regulation in mammals. Here, Cheeseman et al. report dynamic changes in H3K18 PTM during the differentiation stages of Theileria parasites and they identify a SET-domain methyltransferase (TaSETup1) as the relevant enzyme promoting this modification.
Databáze: OpenAIRE