Department of Biochemistry, Stellenbosch University, Stellenbosch 7600, South Africa.
Department of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, and Center for Epigenetics, University of Southern Denmark, Odense M DK-5230, Denmark.
Nucleic Acids Res. 2022 Sep 23;50(17):9705-9723. doi: 10.1093/nar/gkac759.
Trypanosomes diverged from the main eukaryotic lineage about 600 million years ago, and display some unusual genomic and epigenetic properties that provide valuable insight into the early processes employed by eukaryotic ancestors to regulate chromatin-mediated functions. We analysed Trypanosoma brucei core histones by high mass accuracy middle-down mass spectrometry to map core histone post-translational modifications (PTMs) and elucidate cis-histone combinatorial PTMs (cPTMs). T. brucei histones are heavily modified and display intricate cPTMs patterns, with numerous hypermodified cPTMs that could contribute to the formation of non-repressive euchromatic states. The Trypanosoma brucei H2A C-terminal tail is hyperacetylated, containing up to five acetylated lysine residues. MNase-ChIP-seq revealed a striking enrichment of hyperacetylated H2A at Pol II transcription start regions, and showed that H2A histones that are hyperacetylated in different combinations localised to different genomic regions, suggesting distinct epigenetic functions. Our genomics and proteomics data provide insight into the complex epigenetic mechanisms used by this parasite to regulate a genome that lacks the transcriptional control mechanisms found in later-branched eukaryotes. The findings further demonstrate the complexity of epigenetic mechanisms that were probably shared with the last eukaryotic common ancestor.
锥虫大约在 6 亿年前从主要的真核生物谱系中分化出来，表现出一些不寻常的基因组和表观遗传特性，为了解真核生物祖先早期用于调节染色质介导功能的过程提供了有价值的线索。我们通过高质量的中下段质谱分析了布氏锥虫核心组蛋白，以绘制核心组蛋白的翻译后修饰（PTM）图谱，并阐明顺式组蛋白组合 PTM（cPTM）。布氏锥虫组蛋白高度修饰，显示出复杂的 cPTM 模式，具有许多超修饰的 cPTM，可能有助于形成非抑制性常染色质状态。布氏锥虫 H2A C 端尾部高度乙酰化，含有多达五个乙酰化赖氨酸残基。MNase-ChIP-seq 显示，Pol II 转录起始区高度乙酰化的 H2A 明显富集，并且表明以不同组合方式高度乙酰化的 H2A 组蛋白定位于不同的基因组区域，这表明其具有不同的表观遗传功能。我们的基因组学和蛋白质组学数据为了解这种寄生虫用来调节缺乏在后期分支的真核生物中发现的转录控制机制的基因组的复杂表观遗传机制提供了深入的了解。这些发现进一步证明了与最后一个真核生物共同祖先共享的表观遗传机制的复杂性。
