Lopez-Rubio Jose-Juan, Mancio-Silva Liliana, Scherf Artur
Unité de Biologie des Interactions Hôte-Parasite, CNRS URA2581, Institut Pasteur, Paris, France.
Cell Host Microbe. 2009 Feb 19;5(2):179-90. doi: 10.1016/j.chom.2008.12.012.
Clonally variant gene families underlie phenotypic plasticity in Plasmodium falciparum, a process indispensable for survival of the pathogen in its human host. Differential transcription of one of these gene families in clonal parasite lineages has been associated with chromatin modifications. Here, we determine the genome-wide distribution in P. falciparum of a histone mark of heterochromatin, trimethylation of histone H3 lysine 9 (H3K9me3), using high-resolution ChIP-chip analysis. We show that H3K9me3 is specifically associated with clonally variant gene families, which are clustered on subtelomeric and some chromosome internal regions. High levels of H3K9me3 correlate with genes localized to the nuclear periphery, implying chromosome loop formation. Disruption of the histone deacetylase PfSir2 causes changes in H3K9me3 that are discontinuous along chromosomes and associated with disrupted monoallelic transcription. Our data point to the existence of perinuclear repressive centers associated with control of expression of malaria parasite genes involved in phenotypic variation and pathogenesis.
克隆变异基因家族是恶性疟原虫表型可塑性的基础，这一过程对于该病原体在人类宿主中的生存不可或缺。这些基因家族之一在克隆寄生虫谱系中的差异转录与染色质修饰有关。在这里，我们使用高分辨率芯片分析（ChIP-chip）确定了异染色质组蛋白标记——组蛋白H3赖氨酸9三甲基化（H3K9me3）在恶性疟原虫全基因组中的分布。我们发现H3K9me3与克隆变异基因家族特异性相关，这些基因家族聚集在亚端粒和一些染色体内部区域。高水平的H3K9me3与定位于核周边的基因相关，这意味着染色体环的形成。组蛋白去乙酰化酶PfSir2的破坏会导致H3K9me3沿染色体的变化不连续，并与单等位基因转录的破坏相关。我们的数据表明存在与控制参与表型变异和发病机制的疟原虫基因表达相关的核周抑制中心。
