Local regulatory variation in Saccharomyces cerevisiae.
Local regulatory variation in Saccharomyces cerevisiae.
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DOI：
10.1371/journal.pgen.0010025
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发表时间：
2005-08
期刊：
影响因子：
4.5
通讯作者：
Kruglyak L
中科院分区：
文献类型：
--
作者：
Ronald J;Brem RB;Whittle J;Kruglyak L
影响基因表达的自然发生的序列变异是物种内个体间表型差异的重要来源。我们和其他人以前已经表明，这种调控变异既可以发生在与其表达受其影响的基因相同的基因座（局部调控变异），也可以发生在基因组中的其他反式作用因子。在这里，我们提出了一个详细的分析，在酿酒酵母全基因组的局部调控变异。我们使用遗传连锁分析表明，近四分之一的酵母基因包含两个不同菌株之间的局部调控变异。我们测量了两个菌株的二倍体杂种中77个基因的等位基因特异性表达，这些基因显示出强烈的自连锁，并发现在52%-78%的这些基因中，局部调控变异直接顺式起作用。我们还通过实验证实了一个例子，其中AMN 1基因的局部调控变异通过反馈回路反式发挥作用。全基因组序列分析表明，基因的局部调控变异显示增加的多态性的启动子区域，这是由于一些，但不是所有的这种增加是由于预测的转录因子结合位点的多态性。在这些基因的3′非翻译区也发现了增加的多态性。这些发现指出了顺式作用变异的重要性，但也表明，有一套不同的机制，通过局部变异可以影响基因表达水平。基因内部和周围的DNA序列变异可以通过影响基因的表达而导致个体之间的差异。作者已经使用了多种方法来表征这一局部DNA序列变异的大规模在两个菌株的芽殖酵母酿酒酵母。他们的结果表明，相当大一部分基因的表达水平受到局部序列变异的影响。在二倍体杂交酵母中，许多局部变异仅改变两个基因拷贝中的一个的表达，但其他局部变异可以同等地影响两个拷贝。作者还发现，基因附近DNA特定区域的序列变异，包括编码序列的上游和下游，尤其是转录因子结合位点，最有可能影响基因表达。这些结果提供了一个详细的局部序列变异，影响附近的基因在S。啤酒。
Naturally occurring sequence variation that affects gene expression is an important source of phenotypic differences among individuals within a species. We and others have previously shown that such regulatory variation can occur both at the same locus as the gene whose expression it affects (local regulatory variation) and elsewhere in the genome at trans-acting factors. Here we present a detailed analysis of genome-wide local regulatory variation in Saccharomyces cerevisiae. We used genetic linkage analysis to show that nearly a quarter of all yeast genes contain local regulatory variation between two divergent strains. We measured allele-specific expression in a diploid hybrid of the two strains for 77 genes showing strong self-linkage and found that in 52%–78% of these genes, local regulatory variation acts directly in cis. We also experimentally confirmed one example in which local regulatory variation in the gene AMN1 acts in trans through a feedback loop. Genome-wide sequence analysis revealed that genes subject to local regulatory variation show increased polymorphism in the promoter regions, and that some but not all of this increase is due to polymorphisms in predicted transcription factor binding sites. Increased polymorphism was also found in the 3′ untranslated regions of these genes. These findings point to the importance of cis-acting variation, but also suggest that there is a diverse set of mechanisms through which local variation can affect gene expression levels. Variation in DNA sequences in and around a gene can contribute to differences between individuals by affecting the gene's expression. The authors have used a variety of methods to characterize this local DNA sequence variation on a large scale in two strains of the budding yeast Saccharomyces cerevisiae. Their results suggest that the expression levels of a sizeable fraction of genes are affected by local sequence variation. Many local variants alter the expression of only one of two copies of a gene in diploid hybrid yeast, but other local variants can affect both copies equally. The authors also found that sequence variation in particular regions of DNA near genes, both upstream and downstream of coding sequences and especially in transcription factor binding sites, is most likely to affect gene expression. These results provide a detailed view of local sequence variation that affects the expression of nearby genes in S. cerevisiae.
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DOI：
10.1073/pnas.0409159102
发表时间：
2005-01-25
影响因子：
11.1
作者：
Gu, ZL;David, L;Steinmetz, LM
通讯作者：
Steinmetz, LM
影响因子：
30.8
作者：
Cowles, CR;Hirschhorn, JN;Lander, ES
通讯作者：
Lander, ES
影响因子：
7
作者：
Ronald, J;Akey, JM;Kruglyak, L
通讯作者：
Kruglyak, L
影响因子：
7
作者：
Lo, HS;Wang, ZN;Lee, MP
通讯作者：
Lee, MP
影响因子：
30.8
作者：
Bystrykh, L;Weersing, E;de Haan, G
通讯作者：
de Haan, G