Telomeric heterochromatin in Plasmodium falciparum

Abstract

Until very recently, little was known about the chromatin structure of the telomeres and subtelomeric regions in Plasmodium falciparum. In yeast and Drosophila melanogaster, chromatin structure has long been known to be an important aspect in the regulation and functioning of these regions. Telomeres and subtelomeric regions are enriched in epigenetic marks that are specific to heterochromatin, such as methylation of lysine 9 of histone H3 and lysine 20 of histone H4. In P. falciparum, histone modifications and the presence of both the heterochromatin "writing" (PfSir2, PKMT) and "reading" (PfHP1) machinery at telomeric and subtelomeric regions indicate that these regions are likely to have heterochromatic structure that is epigenetically regulated. This structure may be important for telomere functions such as the silencing of the var gene family implicated in the cytoadherence and antigenic variation of these parasites.

Figure 1

A model of P. falciparum chromosome organization. (a) The P. falciparum haploid nuclear genome is organized into 14 linear chromosomes. Each chromosome is composed of an internal region in which housekeeping genes are located, and a chromosome end that displays a higher-order DNA organization common to all P. falciparum chromosomes. Downstream of telomeres resides at highly polymorphic TAS composed of a noncoding and a coding region. The noncoding region contains six TAREs, which are always positioned in the same order but are of variable length. TARE6, also known as Rep20, is responsible for most of the length polymorphism observed in the noncoding region of the TAS. The coding region contains several gene families encoding important virulence factors, such as the var and rifin genes. (b) A schematic representation of post-translational histone modifications in P. falciparum. The amino acids on the N-terminal tails of histone H2A, H2B, H3, H4 and the histone variants H2A.Z and H3.3 that are subject to different modifications are described in the figure.

Figure 2

Hetrochromatin in S. cerevisiae, S. pombe, P. falciparum and human.

Figure 3

Hypothetical model for heterochromatin assembly at P. falciparum chromosome ends. This is a general view of the known chromatin components at P. falciparum subtelomeres. The spreading of heterochromatin along the different TAREs into adjacent coding regions probably involves PfHP1, PfSir2 and PfKMT1 in cooperation. The role of PfOrc1 in this process remains unknown.