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Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum
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, w...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095176/ https://www.ncbi.nlm.nih.gov/pubmed/33839154 http://dx.doi.org/10.1016/j.jbc.2021.100614 |
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author | Jabeena, C.A. Govindaraju, Gayathri Rawat, Mukul Gopi, Soundhararajan Sethumadhavan, Devadathan Valiyamangalath Jaleel, Abdul Sasankan, Dhakshmi Karmodiya, Krishanpal Rajavelu, Arumugam |
author_facet | Jabeena, C.A. Govindaraju, Gayathri Rawat, Mukul Gopi, Soundhararajan Sethumadhavan, Devadathan Valiyamangalath Jaleel, Abdul Sasankan, Dhakshmi Karmodiya, Krishanpal Rajavelu, Arumugam |
author_sort | Jabeena, C.A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8095176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-80951762021-05-13 Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum Jabeena, C.A. Govindaraju, Gayathri Rawat, Mukul Gopi, Soundhararajan Sethumadhavan, Devadathan Valiyamangalath Jaleel, Abdul Sasankan, Dhakshmi Karmodiya, Krishanpal Rajavelu, Arumugam J Biol Chem Research Article 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. American Society for Biochemistry and Molecular Biology 2021-04-09 /pmc/articles/PMC8095176/ /pubmed/33839154 http://dx.doi.org/10.1016/j.jbc.2021.100614 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Jabeena, C.A. Govindaraju, Gayathri Rawat, Mukul Gopi, Soundhararajan Sethumadhavan, Devadathan Valiyamangalath Jaleel, Abdul Sasankan, Dhakshmi Karmodiya, Krishanpal Rajavelu, Arumugam Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum |
title | Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum |
title_full | Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum |
title_fullStr | Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum |
title_full_unstemmed | Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum |
title_short | Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum |
title_sort | dynamic association of the h3k64 trimethylation mark with genes encoding exported proteins in plasmodium falciparum |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095176/ https://www.ncbi.nlm.nih.gov/pubmed/33839154 http://dx.doi.org/10.1016/j.jbc.2021.100614 |
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