Unravelling a histone code for malaria virulence.
Epigenetic phenomena have been shown to play a role in the regulated expression of virulence genes in several pathogenic organisms, including the var gene family in Plasmodium falciparum. A better understanding of how P. falciparum can both maintain a single active var gene locus through many erythrocytic cycles and also achieve successive switching to different loci in order to evade the host immune system is greatly needed. Disruption of this tightly co-ordinated expression system presents an opportunity for increased clearance of the parasites by the immune system and, in turn, reduced mortality and morbidity. In the current issue of Molecular Microbiology, Lopez-Rubio and colleagues investigate the correlation of specific post-translational histone modifications with different transcriptional states of a single var gene, var2csa. Quantitative chromatin immunoprecipitation is used to demonstrate that different histone methylation marks are enriched at the 5' flanking and coding regions of active, poised or silenced var genes. They identify an increase of H3K4me2 and H3K4me3 in the 5' flanking region of an active var locus and expand on an earlier finding that H3K9me3 is enriched in the coding regions of silenced var genes. The authors also present evidence that H3K4me2 bookmarks the active var gene locus during later developmental stages for expression in the subsequent asexual cycle, hinting at a potential mechanism for transcriptional 'memory'. The stage is now set for work generating a complete catalogue of all histone modifications associated with var gene regulation as well as functional studies striving to uncover the precise mechanisms underlying these observations.
Comeaux
Christy A
CA
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Duraisingh
Manoj T
MT
D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics / Q000502:physiology; D014774:Virulence / Q000235:genetics
D006657:Histones; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum