Anderson Letícia, Pierce Raymond J, Verjovski-Almeida Sergio
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-000 São Paulo, SP, Brazil.
Mol Biochem Parasitol. 2012 Jun;183(2):105-14. doi: 10.1016/j.molbiopara.2012.03.001. Epub 2012 Mar 10.
Schistosoma mansoni is a human endoparasite with a complex life cycle that also infects an invertebrate mollusk intermediate host and exhibits many diverse phenotypes. Its complexity is reflected in a large genome and different transcriptome profiles specific to each life cycle stage. Epigenetic regulation of gene expression such as the post-translational modification of histones has a significant impact on phenotypes, and this information storage function resides primarily at histone tails, which results in a varied histone code. Evidence of transcription of the different histone families at all life stages of the parasite was detected by a survey of transcriptome databases; manual curation of each gene prediction at the genome sequence level showed errors in the coding sequences of three of them. The biogenesis of histones is coupled to DNA replication, and a detailed in silico analysis of the specialized machinery of histone mRNA processing in the S. mansoni genome reveals that it is as conserved as in other eukaryotes, consisting in transcription factors and stem-loop binding proteins which recognize the stem loop structure at the histone mRNA 3'UTR. Histone modifying enzymes (HMEs) such as histone acetyltransferases, methyltransferases and deacetylases (HDACs) have been described in S. mansoni, and their potential as new therapeutic targets was evidenced with the apoptotic phenotype that resulted from HDAC inhibition. However, the overall regulation of transcription coupled with gene expression profiles correlated to histone modifications has not yet been characterized. Besides the interaction of HMEs with histones, many factors involved in cellular processes are known to bind to histones, and were identified here by an in silico analysis of the S. mansoni genome. Knowledge of the histone families opens up perspectives for further studies that will lead to a better identification of their post-translational modifications, their gene regulation and to the possible characterization of HMEs as targets for the development of new drugs.
曼氏血吸虫是一种人体寄生虫，其生命周期复杂，还会感染无脊椎动物软体动物中间宿主，并表现出多种不同的表型。其复杂性体现在庞大的基因组以及每个生命周期阶段特定的不同转录组图谱中。基因表达的表观遗传调控，如组蛋白的翻译后修饰，对表型有重大影响，而这种信息存储功能主要存在于组蛋白尾部，从而产生了多样的组蛋白密码。通过对转录组数据库的调查，检测到寄生虫所有生命周期阶段不同组蛋白家族的转录证据；在基因组序列水平对每个基因预测进行人工整理发现其中三个基因的编码序列存在错误。组蛋白的生物合成与DNA复制相关联，对曼氏血吸虫基因组中组蛋白mRNA加工的专门机制进行的详细计算机分析表明，它与其他真核生物一样保守，由识别组蛋白mRNA 3'UTR茎环结构的转录因子和茎环结合蛋白组成。曼氏血吸虫中已描述了组蛋白修饰酶（HMEs），如组蛋白乙酰转移酶、甲基转移酶和脱乙酰酶（HDACs），HDAC抑制导致的凋亡表型证明了它们作为新治疗靶点的潜力。然而，转录与与组蛋白修饰相关的基因表达谱的整体调控尚未得到表征。除了HMEs与组蛋白的相互作用外，许多参与细胞过程的因子已知会与组蛋白结合，在此通过对曼氏血吸虫基因组的计算机分析进行了鉴定。对组蛋白家族的了解为进一步研究开辟了前景，这将有助于更好地鉴定它们的翻译后修饰、基因调控，并可能将HMEs表征为新药开发的靶点。
