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Clipped histone H3 is integrated into nucleosomes of DNA replication genes in the human malaria parasite Plasmodium falciparum .
- Source :
-
EMBO reports [EMBO Rep] 2019 Apr; Vol. 20 (4). Date of Electronic Publication: 2019 Mar 04. - Publication Year :
- 2019
-
Abstract
- 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.<br /> (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)
- Subjects :
- 5' Untranslated Regions
Amino Acid Sequence
Chromatin Immunoprecipitation
Ectopic Gene Expression
Erythrocytes parasitology
Gene Expression Regulation
Histones chemistry
Histones genetics
Humans
Protease Inhibitors pharmacology
Protein Binding
Protein Interaction Domains and Motifs
Proteolysis drug effects
DNA Replication
Histones metabolism
Malaria, Falciparum parasitology
Nucleosomes metabolism
Plasmodium falciparum physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1469-3178
- Volume :
- 20
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- EMBO reports
- Publication Type :
- Academic Journal
- Accession number :
- 30833341
- Full Text :
- https://doi.org/10.15252/embr.201846331