Clipped histone H3 is integrated into nucleosomes of DNA replication genes in the human malaria parasite Plasmodium falciparum

Autor: Herrera‐Solorio, Abril Marcela, Vembar, Shruthi Sridhar, MacPherson, Cameron Ross, Lozano‐Amado, Daniela, Meza, Gabriela Romero, Xoconostle‐Cazares, Beatriz, Martins, Rafael Miyazawa, Chen, Patty, Vargas, Miguel, Scherf, Artur, Hernández‐Rivas, Rosaura
Přispěvatelé: Instituto Politecnico Nacional [Mexico] (IPN), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Consejo Nacional de Ciencia y Tecnología, Mexico (177852), the French‐Mexican collaborative program PARACTIN (ANR‐CONACyT Paractin 140364), and the FOSISS‐CONACyT (272364) awarded to R.H.R. It was also supported by a European Research Council Advanced Grant (PlasmoSilencing 670301) and the French Parasitology consortium ParaFrap (ANR‐11‐LABX0024) awarded to A.S. A.M.H.S. was supported by the Consejo Nacional de Ciencia y Tecnología grant 228896, and S.S.V. was supported by the Carnot‐Pasteur‐Maladies Infectieuse fellowship., ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), European Project: 670301,H2020,ERC-2014-ADG,PlasmoSilencing(2015), Scherf, Artur, Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID, Exoribonuclease-mediated degradation of nascent RNA in Malaria Parasites: A Novel Mechanism in Virulence Gene Silencing - PlasmoSilencing - - H20202015-11-01 - 2020-10-31 - 670301 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: EMBO Reports
EMBO Reports, 2019, 20 (4), pp.e46331. ⟨10.15252/embr.201846331⟩
EMBO Reports, EMBO Press, 2019, 20 (4), pp.e46331. ⟨10.15252/embr.201846331⟩
ISSN: 1469-221X
1469-3178
DOI: 10.15252/embr.201846331⟩
Popis: The fastq files supporting the results of this article are available in the EMBL‐EBI European Nucleotide Archive (ENA: PRJEB18114; Sample group: ERG011046): http://www.ebi.ac.uk/ena/data/view/PRJEB18114.; International audience; Post‐translational modifications of histone H3 N‐terminal tails are key epigenetic regulators of virulence gene expression and sexual commitment in the human malaria parasite Plasmodium falciparum. Here, we identify proteolytic clipping of the N‐terminal tail of nucleosome‐associated histone H3 at amino acid position 21 as a new chromatin modification. A cathepsin C‐like proteolytic clipping activity is observed in nuclear parasite extracts. Notably, an ectopically expressed version of clipped histone H3, PfH3p‐HA, is targeted to the nucleus and integrates into mononucleosomes. Furthermore, chromatin immunoprecipitation and next‐generation sequencing analysis identified PfH3p‐HA as being highly enriched in the upstream region of six genes that play a key role in DNA replication and repair: In these genes, PfH3p‐HA demarcates a specific 1.5 kb chromatin island adjacent to the open reading frame. Our results indicate that, in P. falciparum, the process of histone clipping may precede chromatin integration hinting at preferential targeting of pre‐assembled PfH3p‐containing nucleosomes to specific genomic regions. The discovery of a protease‐directed mode of chromatin organization in P. falciparum opens up new avenues to develop new anti‐malarials.
Databáze: OpenAIRE
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