Histone modifications associated with gene expression and genome accessibility are dynamically enriched at Plasmodium falciparum regulatory sequences.

Autor: Tang J; Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.; School of Medicine, Faculty of Health, Deakin University, Geelong Waurn Ponds Campus, Waurn Ponds, VIC, 3216, Australia., Chisholm SA; School of BioSciences, The University of Melbourne, Parkville, VIC, 3052, Australia.; Bio21 Institute, Parkville, VIC, 3052, Australia., Yeoh LM; Bio21 Institute, Parkville, VIC, 3052, Australia.; Peter Doherty Institute, Melbourne, VIC, 3000, Australia.; Department of Microbiology and Immunology, The University of Melbourne, Victoria, 3000, Australia., Gilson PR; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, VIC, 3004, Australia.; Monash University, Melbourne, VIC, 3800, Australia., Papenfuss AT; Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Mathematics and Statistics, University of Melbourne, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.; Sir Peter MacCallum, Department of Oncology, University of Melbourne, Parkville, VIC, Australia., Day KP; Bio21 Institute, Parkville, VIC, 3052, Australia.; Peter Doherty Institute, Melbourne, VIC, 3000, Australia.; Department of Microbiology and Immunology, The University of Melbourne, Victoria, 3000, Australia., Petter M; Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.; Erlangen University, 91054, Erlangen, Germany., Duffy MF; Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia. mduffy@unimelb.edu.au.; Bio21 Institute, Parkville, VIC, 3052, Australia. mduffy@unimelb.edu.au.; Peter Doherty Institute, Melbourne, VIC, 3000, Australia. mduffy@unimelb.edu.au.; Department of Microbiology and Immunology, The University of Melbourne, Victoria, 3000, Australia. mduffy@unimelb.edu.au.
Jazyk: angličtina
Zdroj: Epigenetics & chromatin [Epigenetics Chromatin] 2020 Nov 23; Vol. 13 (1), pp. 50. Date of Electronic Publication: 2020 Nov 23.
DOI: 10.1186/s13072-020-00365-5
Abstrakt: Background: The malaria parasite Plasmodium falciparum has an unusually euchromatic genome with poorly conserved positioning of nucleosomes in intergenic sequences and poorly understood mechanisms of gene regulation. Variant histones and histone modifications determine nucleosome stability and recruit trans factors, but their combinatorial contribution to gene regulation is unclear.
Results: Here, we show that the histone H3 acetylations H3K18ac and H3K27ac and the variant histone Pf H2A.Z are enriched together at regulatory sites upstream of genes. H3K18ac and H3K27ac together dynamically mark regulatory regions of genes expressed during the asexual life cycle. In contrast, H3K4me1 is depleted in intergenic sequence and dynamically depleted upstream of expressed genes. The temporal pattern of H3K27ac and H3K18ac enrichment indicates that they accumulate during S phase and mitosis and are retained at regulatory sequences until at least G1 phase and after cessation of expression of the cognate genes. We integrated our ChIPseq data with existing datasets to show that in schizont stages H3K18ac, H3K27ac and Pf H2A.Z colocalise with the transcription factor PfAP2-I and the bromodomain protein PfBDP1 and are enriched at stably positioned nucleosomes within regions of exposed DNA at active transcriptional start sites. Using transient transfections we showed that sequences enriched with colocalised H3K18ac, H3K27ac and Pf H2A.Z possess promoter activity in schizont stages, but no enhancer-like activity.
Conclusions: The dynamic H3 acetylations define P. falciparum regulatory sequences and contribute to gene activation. These findings expand the knowledge of the chromatin landscape that regulates gene expression in P. falciparum.
Databáze: MEDLINE
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