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
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