Institute for Advanced Biosciences (IAB), Team Host-pathogen interactions and immunity to infection, INSERM U1209, CNRS UMR5309, Université Grenoble Alpes, Grenoble, France.
Unité de Biologie des Interactions Hôte-Parasite, Institut Pasteur, CNRS, ERL 9195, INSERM, Unit U1201, Paris, France.
Elife. 2017 Nov 4;6:e29391. doi: 10.7554/eLife.29391.
An unusual genome architecture characterizes the two related human parasitic pathogens and A major fraction of the bulk parasite genome is packaged as transcriptionally permissive euchromatin with few loci embedded in silenced heterochromatin. Primary chromatin shapers include histone modifications at the nucleosome lateral surface close to the DNA but their mode of action remains unclear. We now identify versatile modifications at Lys31 within the globular domain of histone H4 that crucially determine genome organization and expression in Apicomplexa parasites. H4K31 acetylation at the promoter correlates with, and perhaps directly regulates, gene expression in both parasites. By contrast, monomethylated H4K31 is enriched in the core body of active genes but inversely correlates with transcription, whereas it is unexpectedly enriched at transcriptionally inactive pericentromeric heterochromatin in , a region devoid of the characteristic H3K9me3 histone mark and its downstream effector HP1.
一种不寻常的基因组结构特征是两种相关的人类寄生虫病原体的特征，大量寄生虫基因组的主要部分被包装为转录允许的常染色质，很少有基因座嵌入沉默的异染色质中。主要的染色质形成体包括核小体侧面表面靠近 DNA 的组蛋白修饰，但它们的作用模式仍不清楚。我们现在确定了组蛋白 H4 球形结构域内 Lys31 上的多功能修饰，这些修饰对顶复门寄生虫的基因组组织和表达至关重要。启动子处的 H4K31 乙酰化与两种寄生虫中的基因表达相关，并且可能直接调节基因表达。相比之下，单甲基化的 H4K31 在活性基因的核心体中富集，但与转录呈负相关，而在转录不活跃的中心体异染色质中却出乎意料地富集，中心体是缺乏特征性 H3K9me3 组蛋白标记及其下游效应物 HP1 的区域。
