Comparative Heterochromatin Profiling Reveals Conserved and Unique Epigenome Signatures Linked to Adaptation and Development of Malaria Parasites

Abstract

SummaryHeterochromatin-dependent gene silencing is central to the adaptation and survival of Plasmodium falciparum malaria parasites, allowing clonally variant gene expression during blood infection in humans. By assessing genome-wide heterochromatin protein 1 (HP1) occupancy, we present a comprehensive analysis of heterochromatin landscapes across different Plasmodium species, strains, and life cycle stages. Common targets of epigenetic silencing include fast-evolving multi-gene families encoding surface antigens and a small set of conserved HP1-associated genes with regulatory potential. Many P. falciparum heterochromatic genes are marked in a strain-specific manner, increasing the parasite's adaptive capacity. Whereas heterochromatin is strictly maintained during mitotic proliferation of asexual blood stage parasites, substantial heterochromatin reorganization occurs in differentiating gametocytes and appears crucial for the activation of key gametocyte-specific genes and adaptation of erythrocyte remodeling machinery. Collectively, these findings provide a catalog of heterochromatic genes and reveal conserved and specialized features of epigenetic control across the genus Plasmodium.

Epigenetic Players of Chromatin Structure Regulation in Plasmodium falciparum

“…[52] Global mapping of HP1 protein across Plasmodium species in various developmental stages identified that the protein is selectively localized to var genes. [54] Further,i ta ssists for heterochromatin formation and chromatin organization for precise gene expression in gametocytes. [54] Also, it has been reported that the acetyl lysine-specific binding bromodomain regulates the expression of invasions pecific genes in P. falciparum.…”

“…[54] Further,i ta ssists for heterochromatin formation and chromatin organization for precise gene expression in gametocytes. [54] Also, it has been reported that the acetyl lysine-specific binding bromodomain regulates the expression of invasions pecific genes in P. falciparum. [55] Therefore, it is evidentt hat the epigenetic modifications and its interacting proteins on am odifiedc hromatin template are highly dynamic through the RBC stages.T he modification-specific interaction of the readerp roteins plays ak ey role in organizing the chromatin structure to maintain the precise gene regulation processes in the malaria parasite.…”

“…The modification specific binding of the PfHP1 chromodomain on nucleosome of the parasite is linked to selective silencing of the var gene expression . Global mapping of HP1 protein across Plasmodium species in various developmental stages identified that the protein is selectively localized to var genes . Further, it assists for heterochromatin formation and chromatin organization for precise gene expression in gametocytes .…”

“…The nature of the organization of the parasite genome in these stages is largely unknown. Most of the chromatin exists as euchromatic in actively growing trophozoite stage and forms stable heterochromatic structures in few regions during ring, schizont and gametocyte stages . The chromatin structure of P. falciparum is dynamic and it has been shown that the genome contains poorly positioned nucleosomes that are highly accessible .…”

Sex in Plasmodium falciparum: Silence Play between GDV1 and HP1

“…[8] have demonstrated that heterochromatin features marked by HP1 are conserved in the differentiating gametocytes of several Plasmodium species, and showed that epigenomic patterns are linked to various stages of parasite development. A similar analysis by Bunnik et al .…”