title: Dynamic histone H3 epigenome marking during the intraerythrocytic cycle of Plasmodium falciparum.
abstract: Epigenome profiling has led to the paradigm that promoters of active genes are decorated with H3K4me3 and H3K9ac marks. To explore the epigenome of Plasmodium falciparum asexual stages, we performed MS analysis of histone modifications and found a general preponderance of H3/H4 acetylation and H3K4me3. ChIP-on-chip profiling of H3, H3K4me3, H3K9me3, and H3K9ac from asynchronous parasites revealed an extensively euchromatic epigenome with heterochromatin restricted to variant surface antigen gene families (VSA) and a number of genes hitherto unlinked to VSA. Remarkably, the vast majority of the genome shows an unexpected pattern of enrichment of H3K4me3 and H3K9ac. Analysis of synchronized parasites revealed significant developmental stage specificity of the epigenome. In rings, H3K4me3 and H3K9ac are homogenous across the genes marking active and inactive genes equally, whereas in schizonts, they are enriched at the 5' end of active genes. This study reveals an unforeseen and unique plasticity in the use of the epigenetic marks and implies the presence of distinct epigenetic pathways in gene silencing/activation throughout the erythrocytic cycle.
authors.affiliation: Department of Molecular Biology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen, The Netherlands.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Salcedo-Amaya
authors.forename: Marc A
authors.initials: MA
authors.lastname: van Driel
authors.forename: Blaise T
authors.initials: BT
authors.lastname: Alako
authors.forename: Morten B
authors.initials: MB
authors.lastname: Trelle
authors.forename: Antonia M G
authors.initials: AM
authors.lastname: van den Elzen
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Cohen
authors.forename: Eva M
authors.initials: EM
authors.lastname: Janssen-Megens
authors.forename: Marga
authors.initials: M
authors.lastname: van de Vegte-Bolmer
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Selzer
authors.forename: A Leonardo
authors.initials: AL
authors.lastname: Iniguez
authors.forename: Roland D
authors.initials: RD
authors.lastname: Green
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.forename: Ole N
authors.initials: ON
authors.lastname: Jensen
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D004912:Erythrocytes / Q000469:parasitology*; D018503:Genome, Protozoan; D006570:Heterochromatin / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D013058:Mass Spectrometry; D020411:Oligonucleotide Array Sequence Analysis; D010963:Plasmodium falciparum / Q000235:genetics* / Q000502:physiology
chemical_list: D006570:Heterochromatin; D006657:Histones