Epigenetic regulation of the Plasmodium falciparum genome

Abstract

Recent research has highlighted some unique aspects of chromatin biology in the malaria parasite Plasmodium falciparum. During its erythrocytic lifecycle P. falciparum maintains its genome primarily as unstructured euchromatin. Indeed there is no clear role for chromatin-mediated silencing of the majority of the developmentally expressed genes in P. falciparum. However discontinuous stretches of heterochromatin are critical for variegated expression of contingency genes that mediate key pathogenic processes in malaria. These range from invasion of erythrocytes and antigenic variation to solute transport and growth adaptation in response to environmental changes. Despite lack of structure within euchromatin the nucleus maintains functional compartments that regulate expression of many genes at the nuclear periphery, particularly genes with clonally variant expression. The typical components of the chromatin regulatory machinery are present in P. falciparum; however, some of these appear to have evolved novel species-specific functions, e.g. the dynamic regulation of histone variants at virulence gene promoters. The parasite also appears to have repeatedly acquired chromatin regulatory proteins through lateral transfer from endosymbionts and from the host. P. falciparum chromatin regulators have been successfully targeted with multiple drugs in laboratory studies; hopefully their functional divergence from human counterparts will allow the development of parasite-specific inhibitors.

Single-molecule analysis reveals that DNA replication dynamics vary across the course of schizogony in the malaria parasite Plasmodium falciparum

“…P . falciparum uses most of the canonical epigenetic histone marks 49 , some of which could contribute to origin specification, whereas guanine quadruplexes are an unlikely player because they are predicted to be much too rare, with only ~80 occurring outside the telomeres in this highly A/T-rich genome 50, 51 . However, poly-A/T tracts are contrastingly common 32 and these are involved in origin specification in fission yeast 52 and in Xenopus 53 .…”

A Plasmodium Falciparum Bromodomain Protein Regulates Invasion Gene Expression

“…Chromatin-based regulation of gene expression is known to be important in regulating key pathogenic processes in P. falciparum (Duffy et al, 2014). This has been best studied in the var multigene family of immunodominant variant antigens (Duraisingh et al, 2005;Freitas-Junior et al, 2005;Petter et al, 2011;Volz et al, 2012).…”

Transcriptional Profiling Defines Histone Acetylation as a Regulator of Gene Expression during Human-to-Mosquito Transmission of the Malaria Parasite Plasmodium falciparum

“…To date, histone PTMs were particularly studied during the expression of virulence-associated clonally variant multigene families, like the var gene family, which encodes the P. falciparum erythrocyte membrane protein PfEMP1 (Lopez-Rubio et al, 2007, 2009; Petter et al, 2011; reviewed in Llinás et al, 2008; Cui and Miao, 2010; Duffy et al, 2014; Duraisingh and Horn, 2016). Only a single var gene is expressed during replication of the RBC parasites at any one time, whereas all other var genes remain silent.…”