Epigenetic landscapes underlining global patterns of gene expression in the human malaria parasite, Plasmodium falciparum.

The dynamic chromatin landscape displaying combinatorial complexity of the epigenome impacts gene expression that underlies many events of differentiation and cell cycle progression. In the past few years, epigenetic mechanisms have emerged as important processes involved in the tight gene regulation in malaria parasites, Plasmodium spp. Focusing predominantly on Plasmodium falciparum, the species associated with the most severe form of the disease, many advances have been made in our understanding of the interaction between transcriptional regulation and epigenetic mechanisms as the pivotal processes in regulating life cycle progression, host parasite interactions and parasite adaptation to the host environment. This review focuses on the epigenome and its effect on transcriptional regulation in P. falciparum, highlighting its unique, evolutionary diverse features.

Histone 4 lysine 8 acetylation regulates proliferation and host-pathogen interaction in Plasmodium falciparum.

BACKGROUND: The dynamics of histone modifications in Plasmodium falciparum indicates the existence of unique mechanisms that link epigenetic factors with transcription. Here, we studied the impact of acetylated histone code on transcriptional regulation during the intraerythrocytic developmental cycle (IDC) of P. falciparum. RESULTS: Using a dominant-negative transgenic approach, we showed that acetylations of histone H4 play a direct role in transcription. Specifically, these histone modifications mediate an inverse transcriptional relationship between the factors of cell proliferation and host-parasite interaction. Out of the four H4 acetylations, H4K8ac is likely the rate-limiting, regulatory step, which modulates the overall dynamics of H4 posttranslational modifications. H4K8ac exhibits maximum responsiveness to HDAC inhibitors and has a highly dynamic distribution pattern along the genome of P. falciparum during the IDC. Moreover, H4K8ac functions mainly in the euchromatin where its occupancy shifts from intergenic regions located upstream of 5' end of open reading frame into the protein coding regions. This shift is directly or indirectly associated with transcriptional activities at the corresponding genes. H4K8ac is also active in the heterochromatin where it stimulates expression of the main antigenic gene family (var) by its presence in the promoter region. CONCLUSIONS: Overall, we demonstrate that H4K8ac is a potential major regulator of chromatin-linked transcriptional changes during P. falciparum life cycle which is associated not only with euchromatin but also with heterochromatin environment. This is potentially a highly significant finding that suggests a regulatory connection between growth and parasite-host interaction both of which play a major role in malaria parasite virulence.