Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum
Autor: | Gayathri Govindaraju, Devadathan Valiyamangalath Sethumadhavan, Mukul Rawat, Soundhararajan Gopi, C.A. Jabeena, Krishanpal Karmodiya, Dhakshmi Sasankan, Arumugam Rajavelu, Abdul Jaleel |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Erythrocytes IDC intra-erythrocytic developmental cycle Plasmodium falciparum malaria Protozoan Proteins exported family proteins Biochemistry SET Su (var) 3-9 Enhancer-of-zeste and Trithorax Histones 03 medical and health sciences PDB Protein Data Bank parasitic diseases Histone methylation Gene expression Humans Nucleosome histone methylation Epigenetics Malaria Falciparum Molecular Biology Gene 030102 biochemistry & molecular biology biology Lysine nucleosome H3K64 histone 3 at lysine 64 Cell Biology DNA Methylation biology.organism_classification Nucleosomes Cell biology ChIP chromatin immunoprecipitation Histone Code 030104 developmental biology Histone H3K64me3 trimethylation at lysine 64 on histone 3 RBCs red blood cells biology.protein PfSET Plasmodium falciparum Su (var) 3-9 Enhancer Chromatin immunoprecipitation Research Article |
Zdroj: | The Journal of Biological Chemistry |
ISSN: | 0021-9258 |
DOI: | 10.1016/j.jbc.2021.100614 |
Popis: | Epigenetic modifications have emerged as critical regulators of virulence genes and stage-specific gene expression in Plasmodium falciparum. However, the specific roles of histone core epigenetic modifications in regulating the stage-specific gene expression are not well understood. In this study, we report an unconventional trimethylation at lysine 64 on histone 3 (H3K64me3) and characterize its functional relevance in P. falciparum. We show that PfSET4 and PfSET5 proteins of P. falciparum methylate H3K64 and that they prefer the nucleosome as a substrate over free histone 3 proteins. Structural analysis of PfSET5 revealed that it interacts with the nucleosome as a dimer. The H3K64me3 mark is dynamic, being enriched in the ring and trophozoite stages and drastically reduced in the schizont stages. Stage-specific global chromatin immunoprecipitation -sequencing analysis of the H3K64me3 mark revealed the selective enrichment of this methyl mark on the genes of exported family proteins in the ring and trophozoite stages and a significant reduction of the same in the schizont stages. Collectively, our data identify a novel epigenetic mark that is associated with the subset of genes encoding for exported proteins, which may regulate their expression in different stages of P. falciparum. |
Databáze: | OpenAIRE |
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