Previously Unidentified Histone H1-Like Protein Is Involved in Cell Division and Ribosome Biosynthesis in Toxoplasma gondii.
Previously Unidentified Histone H1-Like Protein Is Involved in Cell Division and Ribosome Biosynthesis in Toxoplasma gondii.
复制标题
作者：
染色质动力学可以调节所有依赖DNA的过程。进入染色质内的DNA主要由组蛋白及其翻译后修饰（PTM）协调。与其他真核生物一样，顶复门寄生虫弓形虫编码四种典型组蛋白和五种组蛋白变体。相反，连接组蛋白（H1）从未在顶复门寄生虫中发现。在其他真核生物中，组蛋白H1通过连接核小体和增加DNA压缩来压缩染色质。H1是一种多功能蛋白质，可以参与DNA代谢的不同步骤或与不同生物过程相关的蛋白质复合物相关。我们在T.弓形虫（“TgH 1样”），尽管缺乏哺乳动物H1的球状结构域，但与细菌和锥虫的H1样蛋白非常相似。我们的研究结果表明，TgH 1-like是一种与染色质和其他组蛋白相关的核蛋白。奇怪的是，TgH 1样蛋白也存在于核仁中，并与核糖体蛋白相关，表明这种寄生虫具有多种功能。虽然tgh 1-like基因的敲除不影响细胞周期，但它会导致内源性多聚体和异步分裂。有趣的是，后修饰氨基酸的突变导致细胞分裂缺陷，如Δ tgh 1样突变体中的缺陷，表明这些位点对蛋白质功能很重要。此外，在缓殖子阶段，这种蛋白质仅在分裂的寄生虫中表达，加强了其在细胞分裂中的重要性。事实上，TgH 1样蛋白的缺失降低了外周染色质的致密化，证实了其在T.刚地。重要性组蛋白H1，或连接组蛋白，是一种重要的蛋白质，结合到核小体，帮助染色质压实。在这里，我们第一次在T。弓形虫，命名为TgH 1样。它是一种小的碱性蛋白，仅对应于人类H1的C-末端部分，但与锥虫和细菌的组蛋白H1相似。TgH 1样蛋白位于细胞核中，与核小体组蛋白相互作用，并在染色质结构和细胞分裂中起作用。我们的研究结果首次显示了组蛋白H1蛋白在顶复门寄生虫中的存在，并将为T.弓形虫和相关寄生虫。
Chromatin dynamics can regulate all DNA-dependent processes. Access to DNA within chromatin is orchestrated mainly by histones and their posttranslational modifications (PTMs). Like other eukaryotes, the apicomplexan parasite Toxoplasma gondii encodes four canonical histones and five histone variants. In contrast, the linker histone (H1) has never been identified in apicomplexan parasites. In other eukaryotes, histone H1 compacts the chromatin by linking the nucleosome and increasing the DNA compaction. H1 is a multifunctional protein and can be involved in different steps of DNA metabolism or associated with protein complexes related to distinct biological processes. We have identified a novel protein in T. gondii (“TgH1-like”) that, although lacking the globular domain of mammalian H1, is remarkably like the H1-like proteins of bacteria and trypanosomatids. Our results demonstrate that TgH1-like is a nuclear protein associated with chromatin and other histones. Curiously, TgH1-like is also in the nucleolus and associated with ribosomal proteins, indicating a versatile function in this parasite. Although knockout of the tgh1-like gene does not affect the cell cycle, it causes endopolygeny and asynchronous division. Interestingly, mutation of posttranslationally modified amino acids results in defects in cell division like those in the Δtgh1-like mutant, showing that these sites are important for protein function. Furthermore, in the bradyzoite stage, this protein is expressed only in dividing parasites, reinforcing its importance in cell division. Indeed, the absence of TgH1-like decreases compaction of peripheral chromatin, confirming its role in the chromatin modulation in T. gondii. IMPORTANCE Histone H1, or linker histone, is an important protein that binds to the nucleosome, aiding chromatin compaction. Here, we characterize for the first time a linker histone in T. gondii, named TgH1-like. It is a small and basic protein that corresponds only to the C-terminal portion of the human H1 but is similar to histone H1 from trypanosomatids and bacteria. TgH1-like is located in the nucleus, interacts with nucleosome histones, and acts in chromatin structure and cell division. Our findings show for the first time the presence of a histone H1 protein in an apicomplexan parasite and will provide new insights into cell division and chromatin dynamics in T. gondii and related parasites.
登录
查看更多内容
影响因子：
14.9
作者：
Harshman SW;Young NL;Parthun MR;Freitas MA
通讯作者：
Freitas MA
影响因子：
14.9
作者：
Goujon M;McWilliam H;Li W;Valentin F;Squizzato S;Paern J;Lopez R
通讯作者：
Lopez R
影响因子：
14.9
作者：
Balaji S;Babu MM;Iyer LM;Aravind L
通讯作者：
Aravind L
影响因子：
1.5
作者：
Gubbels, MJ;Wieffer, M;Striepen, B
通讯作者：
Striepen, B
影响因子：
--
作者：
Huynh, My-Hang;Carruthers, Vern B.
通讯作者：
Carruthers, Vern B.