Mutational sources of trans-regulatory variation affecting gene expression in Saccharomyces cerevisiae.
Mutational sources of trans-regulatory variation affecting gene expression in Saccharomyces cerevisiae.
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DOI：
10.7554/elife.67806
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发表时间：
2021-08-31
期刊：
影响因子：
7.7
通讯作者：
Wittkopp PJ
中科院分区：
文献类型：
--
作者：
Duveau F;Vande Zande P;Metzger BP;Diaz CJ;Walker EA;Tryban S;Siddiq MA;Yang B;Wittkopp PJ
基因表达的可遗传变异源于影响其调控网络的顺式和反式组分的突变。在这里，我们通过鉴定和表征69个突变，研究了反调控突变是如何在基因组和基因调控网络中分布的，这些突变对酿酒酵母中同一局灶基因的表达具有反调控作用。相对于不影响该局灶基因表达的1766个突变，我们发现这些反调控突变在先前预测的调节局灶基因表达的转录因子编码序列中富集。然而，超过90%的反调控突变与其他类型的基因相关，包括染色质状态、代谢和信号转导等多种生物过程。这些数据显示了不同类型基因的遗传变化如何影响基因在反式中的表达，揭示了反式调控突变的特性，为自然种群中反式调控变异的分离提供了原材料。
Heritable variation in a gene’s expression arises from mutations impacting cis- and trans-acting components of its regulatory network. Here, we investigate how trans-regulatory mutations are distributed within the genome and within a gene regulatory network by identifying and characterizing 69 mutations with trans-regulatory effects on expression of the same focal gene in Saccharomyces cerevisiae. Relative to 1766 mutations without effects on expression of this focal gene, we found that these trans-regulatory mutations were enriched in coding sequences of transcription factors previously predicted to regulate expression of the focal gene. However, over 90% of the trans-regulatory mutations identified mapped to other types of genes involved in diverse biological processes including chromatin state, metabolism, and signal transduction. These data show how genetic changes in diverse types of genes can impact a gene’s expression in trans, revealing properties of trans-regulatory mutations that provide the raw material for trans-regulatory variation segregating within natural populations.