新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » BIOON报道 » PLOS Genetics:删除真菌中基因kmt6有助发现新的抗生素

PLOS Genetics:删除真菌中基因kmt6有助发现新的抗生素

来源:生物谷 2013-11-03 21:18

2013年11月2日讯 /生物谷BIOON/--近日,俄勒冈州立大学研究人员发现,常见真菌的一个基因充当“主调节器”,删除它后有助发现新化合物,寻找潜在新的抗生素。

这一研究发现已经发表在PLOS Genetics杂志上。科学家成功地翻转了一种遗传开关,这一遗传开关沉默真菌中超过2000个基因。在实验室中,许多真菌的基因组大约有三分之一是一直沉默的,俄勒冈州立大学的科学学院生物化学和生物物理学副教授Michael Freitag说:许多真菌具有抗菌性能。

研究人员还没有能够打开这些真菌更多的基因组,来全方位的分析这些基因表达产生的化合物。在过去,寻找新的抗生素,通常通过改变真菌或其他生命生长的环境,然后判断环境的变化所形成的新化合物是否具有抗生素特性。

传统的寻找抗生素的方法效率低,但现在,研究人员可以改变真菌全基因组表达,可能寻找到以前甚至不知道存在的大量化合物。

研究人员发现:突变后不表达这种基因允许真菌创建新的基因表达,或使得真菌基因组大约25%的基因过度表达,并形成许多次生代谢产物。

研究人员说,被删除的基因kmt6编码一个“主调节器”,后者影响数以百计的遗传信息表达,它在多种生命形式如植物,真菌,果蝇和人类保存了数百万年。研究人员说,由于细菌,寄生虫和真菌的抗药性越来越强,开发新抗生素的重要性与日俱增。

新研究将有助利用基因簇表观遗传工程,产生生物活性化合物如公认的霉菌毒素,抗生素和工业原料。(生物谷Bioon.com)

The Fusarium graminearum Histone H3 K27 Methyltransferase KMT6 Regulates Development and Expression of Secondary Metabolite Gene Clusters

Lanelle R. Connolly, Kristina M. Smith, Michael Freitag

The cereal pathogen Fusarium graminearum produces secondary metabolites toxic to humans and animals, yet coordinated transcriptional regulation of gene clusters remains largely a mystery. By chromatin immunoprecipitation and high-throughput DNA sequencing (ChIP-seq) we found that regions with secondary metabolite clusters are enriched for trimethylated histone H3 lysine 27 (H3K27me3), a histone modification associated with gene silencing. H3K27me3 was found predominantly in regions that lack synteny with other Fusarium species, generally subtelomeric regions. Di- or trimethylated H3K4 (H3K4me2/3), two modifications associated with gene activity, and H3K27me3 are predominantly found in mutually exclusive regions of the genome. To find functions for H3K27me3, we deleted the gene for the putative H3K27 methyltransferase, KMT6, a homolog of Drosophila Enhancer of zeste, E(z). The kmt6 mutant lacks H3K27me3, as shown by western blot and ChIP-seq, displays growth defects, is sterile, and constitutively expresses genes for mycotoxins, pigments and other secondary metabolites. Transcriptome analyses showed that 75% of 4,449 silent genes are enriched for H3K27me3. A subset of genes that were enriched for H3K27me3 in WT gained H3K4me2/3 in kmt6. A largely overlapping set of genes showed increased expression in kmt6. Almost 95% of the remaining 2,720 annotated silent genes showed no enrichment for either H3K27me3 or H3K4me2/3 in kmt6. In these cases mere absence of H3K27me3 was insufficient for expression, which suggests that additional changes are required to activate genes. Taken together, we show that absence of H3K27me3 allowed expression of an additional 14% of the genome, resulting in derepression of genes predominantly involved in secondary metabolite pathways and other species-specific functions, including putative secreted pathogenicity factors. Results from this study provide the framework for novel targeted strategies to control the “cryptic genome”, specifically secondary metabolite expression.

 

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库