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

Cell Host Microbe. 2018 Mar 14;23(3):407-420.e8. doi: 10.1016/j.chom.2018.01.008. Epub 2018 Mar 1.

Abstract

Heterochromatin-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.

Keywords: HP1; Plasmodium; antigenic variation; epigenetics; gametocytes; gene silencing; heterochromatin; host-parasite interaction; malaria; sexual differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / genetics
  • Adaptation, Physiological / physiology
  • Animals
  • Antigenic Variation / genetics
  • Antigens, Protozoan / genetics
  • Cell Proliferation
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Disease Models, Animal
  • Epigenesis, Genetic / genetics*
  • Epigenomics*
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Gene Silencing
  • Heterochromatin / genetics*
  • Host-Parasite Interactions / genetics
  • Host-Parasite Interactions / physiology
  • Humans
  • Life Cycle Stages / genetics
  • Life Cycle Stages / physiology
  • Malaria, Falciparum / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Parasites / genetics
  • Phylogeny
  • Plasmodium / classification
  • Plasmodium / genetics*
  • Plasmodium / physiology*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / metabolism
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Sex Differentiation

Substances

  • Antigens, Protozoan
  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • Protozoan Proteins
  • Chromobox Protein Homolog 5