Genetic analysis of variation in transcription factor binding in yeast.
Genetic analysis of variation in transcription factor binding in yeast.
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作者：
转录调控的变异被认为是表型多样性的主要原因。尽管已经观察到一个物种个体之间基因表达存在广泛差异，但很少有研究检查转录因子（TF）结合的变异性，因此 TF 结合多样性的程度和潜在遗传基础在很大程度上是未知的。在这项研究中，我们绘制了个体之间转录结合的差异，并在全基因组范围内阐明了这种变异的遗传基础。使用 ChIP Seq 在经过信息素处理的细胞中测定全基因组 Ste12 结合谱，这些细胞是两个高度分化的酵母菌株及其亲本系之间杂交的 43 个分离子。我们发现了个体之间广泛的 Ste12 结合变异，并绘制了导致这种变异的潜在顺式和反式基因座。我们表明，大多数 TF 结合变异是顺式连接的，并且许多变异与 Ste12 以及几个提出的 Ste12 辅因子的结合基序中的多态性相关。我们还鉴定了两种反式因子 AMN1 和 FLO8，它们在 α 因子处理下调节 Ste12 与 10 多个基因的启动子的结合。之前并不知道这两个基因会调节 Ste12，我们认为它们可能是基因活性和表型多样性的调节者。 Ste12 结合与 200 多个基因的基因表达密切相关，表明结合变异是有功能的。许多可变结合基因参与细胞壁组织和生物发生。总的来说，这些研究确定了个体分子多样性的遗传调节因子，并为基因调节机制提供了新的见解。
Variation in transcriptional regulation is thought to be a major cause of phenotypic diversity. Although widespread differences in gene expression among individuals of a species have been observed, few studies have examined the variability of transcription factor (TF) binding, and thus the extent and underlying genetic basis of TF binding diversity is largely unknown. In this study, we mapped differences in transcription binding among individuals and elucidated the genetic basis of such variation on a genome-wide scale. Whole-genome Ste12 binding profiles were determined using ChIP Seq in pheromone-treated cells of 43 segregants of a cross between two highly diverged yeast strains and their parental lines. We identified extensive Ste12 binding variation among individuals and mapped underlying cis- and trans- acting loci responsible for such variation. We showed that the majority of TF binding variation is cis-linked and that many variations are associated with polymorphisms residing in the binding motifs of Ste12 as well as those of several proposed Ste12 cofactors. We also identified two trans factors, AMN1 and FLO8, that modulate Ste12 binding to promoters of more than 10 genes under α-factor treatment. Neither of these two genes was known to regulate Ste12 previously, and we suggest that they may be mediators of gene activity and phenotypic diversity. Ste12 binding strongly correlates with gene expression for more than 200 genes indicating that binding variation is functional. Many of the variable bound genes are involved in cell wall organization and biogenesis. Overall these studies identified genetic regulators of molecular diversity among individuals and provide novel insights into mechanisms of gene regulation.
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影响因子：
--
作者：
Aparicio, Oscar;Geisberg, Joseph V;Struhl, Kevin
通讯作者：
Struhl, Kevin
DOI：
10.1007/bf00259671
发表时间：
1991-06-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
HWANGSHUM, JJ;HAGEN, DC;SPRAGUE, GF
通讯作者：
SPRAGUE, GF
影响因子：
5.3
作者：
GIMENO, CJ;FINK, GR
通讯作者：
FINK, GR
影响因子：
64.8
作者：
Mancera, Eugenio;Bourgon, Richard;Brozzi, Alessandro;Huber, Wolfgang;Steinmetz, Lars M.
通讯作者：
Steinmetz, Lars M.
影响因子：
46.9
作者：
Rozowsky, Joel;Euskirchen, Ghia;Auerbach, Raymond K.;Zhang, Zhengdong D.;Gibson, Theodore;Bjornson, Robert;Carriero, Nicholas;Snyder, Michael;Gerstein, Mark B.
通讯作者：
Gerstein, Mark B.