Dynamic and Combinatorial Landscape of Histone Modifications during the Intraerythrocytic Developmental Cycle of the Malaria Parasite.
A major obstacle in understanding the complex biology of the malaria parasite remains to discover how gene transcription is controlled during its life cycle. Accumulating evidence indicates that the parasite's epigenetic state plays a fundamental role in gene expression and virulence. Using a comprehensive and quantitative mass spectrometry approach, we determined the global and dynamic abundance of histones and their covalent post-transcriptional modifications throughout the intraerythrocytic developmental cycle of Plasmodium falciparum. We detected a total of 232 distinct modifications, of which 160 had never been detected in Plasmodium and 88 had never been identified in any other species. We further validated over 10% of the detected modifications and their expression patterns by multiple reaction monitoring assays. In addition, we uncovered an unusual chromatin organization with parasite-specific histone modifications and combinatorial dynamics that may be directly related to transcriptional activity, DNA replication, and cell cycle progression. Overall, our data suggest that the malaria parasite has a unique histone modification signature that correlates with parasite virulence.
Stowers Institute for Medical Research , 1000 E. 50th Street, Kansas City, Missouri 64110, United States.
Anita
A
Saraf
Department of Cell Biology and Neuroscience, University of California , 900 University Avenue, Riverside, California 92521, United States.
Serena
S
Cervantes
Department of Cell Biology and Neuroscience, University of California , 900 University Avenue, Riverside, California 92521, United States.
Evelien M
EM
Bunnik
Department of Cell Biology and Neuroscience, University of California , 900 University Avenue, Riverside, California 92521, United States.
Nadia
N
Ponts
Stowers Institute for Medical Research , 1000 E. 50th Street, Kansas City, Missouri 64110, United States.
Mihaela E
ME
Sardiu
Department of Cell Biology and Neuroscience, University of California , 900 University Avenue, Riverside, California 92521, United States.
Duk-Won D
DW
Chung
Department of Cell Biology and Neuroscience, University of California , 900 University Avenue, Riverside, California 92521, United States.
Jacques
J
Prudhomme
Stowers Institute for Medical Research , 1000 E. 50th Street, Kansas City, Missouri 64110, United States.
Joseph M
JM
Varberg
Stowers Institute for Medical Research , 1000 E. 50th Street, Kansas City, Missouri 64110, United States.
Zhihui
Z
Wen
Stowers Institute for Medical Research , 1000 E. 50th Street, Kansas City, Missouri 64110, United States.|Department of Pathology and Laboratory Medicine, University of Kansas Medical Center , 3901 Rainbow Boulevard, Kansas City, Kansas 66160, United States.
Michael P
MP
Washburn
Stowers Institute for Medical Research , 1000 E. 50th Street, Kansas City, Missouri 64110, United States.
Laurence
L
Florens
Department of Cell Biology and Neuroscience, University of California , 900 University Avenue, Riverside, California 92521, United States.
Karine G
KG
Le Roch
D044127:Epigenesis, Genetic; D004912:Erythrocytes / Q000469:parasitology; D042421:Histone Code; D006657:Histones / Q000378:metabolism; D008018:Life Cycle Stages / Q000235:genetics*; D008288:Malaria / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000235:genetics / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000009:adverse effects / Q000032:analysis; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D006657:Histones; D015800:Protozoan Proteins
cell cycle; epigenetics; histones; label-free quantification; malaria; multiple reaction monitoring; parasite; post-translational modifications; tandem mass spectrometry