Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum

TY - JOUR

T1 - Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum

AU - Jabeena, C. A.

AU - Govindaraju, Gayathri

AU - Rawat, Mukul

AU - Gopi, Soundhararajan

AU - Sethumadhavan, Devadathan Valiyamangalath

AU - Jaleel, Abdul

AU - Sasankan, Dhakshmi

AU - Karmodiya, Krishanpal

AU - Rajavelu, Arumugam

N1 - Publisher Copyright: © 2021 THE AUTHORS.

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85104656047

U2 - 10.1016/j.jbc.2021.100614

DO - 10.1016/j.jbc.2021.100614

M3 - Article

C2 - 33839154

AN - SCOPUS:85104656047

SN - 0021-9258

VL - 296

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

M1 - 100614

ER -