Transcriptome Analysis in Yeast Reveals the Externality of Position Effects.
Transcriptome Analysis in Yeast Reveals the Externality of Position Effects.
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酵母转录组分析揭示位置效应的外部性
DOI：
10.1093/molbev/msab104
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发表时间：
2021-07-29
影响因子：
10.7
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Gui Q;Deng S;Zhou Z;Cao W;Zhang X;Shi W;Cai X;Jiang W;Cui Z;Hu Z;Chen X
新整合到染色体中的基因的活性取决于整合位点的基因组背景。这种“位置效应”已被广泛报道，尽管硬币的另一面，即整合如何影响局部染色体环境，仍然在很大程度上未被探索，位置效应的这种“外部性”的机制和表型后果也是如此。在这里，我们研究了大约250个酿酒酵母菌株的转录组图谱，每个菌株都将GFP整合到野生型菌株的不同位点。我们发现，在富含必需基因的基因组区域，GFP表达倾向于较低，并且整合位点附近的基因倾向于显示更大的表达降低。与公开的全基因组蛋白修饰谱的进一步联合分析表明，这种效应与H3K4me2相关。更重要的是，我们发现邻近基因表达的变化，而不是GFP表达，显着改变了细胞的生长速度。结果，在整合后立即显示高GFP表达的基因组位点与由邻近基因的表达升高引起的生长劣势相关，最终导致长期的低GFP总产量。我们的研究结果与相邻基因之间对转录资源的竞争一致，并揭示了位置效应的一个以前未被重视的方面。这项研究突出了位置效应对外源基因整合的命运的影响，并对生物工程和病毒整合到宿主基因组中的病理学具有重要意义。
The activity of a gene newly integrated into a chromosome depends on the genomic context of the integration site. This “position effect” has been widely reported, although the other side of the coin, that is, how integration affects the local chromosomal environment, has remained largely unexplored, as have the mechanism and phenotypic consequences of this “externality” of the position effect. Here, we examined the transcriptome profiles of approximately 250 Saccharomyces cerevisiae strains, each with GFP integrated into a different locus of the wild-type strain. We found that in genomic regions enriched in essential genes, GFP expression tended to be lower, and the genes near the integration site tended to show greater expression reduction. Further joint analysis with public genome-wide histone modification profiles indicated that this effect was associated with H3K4me2. More importantly, we found that changes in the expression of neighboring genes, but not GFP expression, significantly altered the cellular growth rate. As a result, genomic loci that showed high GFP expression immediately after integration were associated with growth disadvantages caused by elevated expression of neighboring genes, ultimately leading to a low total yield of GFP in the long run. Our results were consistent with competition for transcriptional resources among neighboring genes and revealed a previously unappreciated facet of position effects. This study highlights the impact of position effects on the fate of exogenous gene integration and has significant implications for biological engineering and the pathology of viral integration into the host genome.
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