The Role of Transcription Factors at Antisense-Expressing Gene Pairs in Yeast.
The Role of Transcription Factors at Antisense-Expressing Gene Pairs in Yeast.
复制标题
DOI：
10.1093/gbe/evw104
复制
发表时间：
2016-06-27
影响因子：
3.3
通讯作者：
Brem RB
中科院分区：
文献类型：
--
作者：
Mostovoy Y;Thiemicke A;Hsu TY;Brem RB
染色体上彼此靠近编码的基因通常通过一种仍知之甚少的机制和调控逻辑共表达。我们调查了酵母基因组中尾对头定向的串联基因对，其中上游基因的反义表达在物种间是保守的。大多数此类串联对的基因间区域是双向启动子，由下游基因 mRNA 和上游反义转录物共享。这些基因间位点的基因组分析揭示了转录因子调控的独特模式。给定转录因子的突变验证了其作为串联基因对基因座反式调节剂的作用，包括近端起始上游反义转录物和下游mRNA以及远端起始上游mRNA。为了研究该位点的顺式调节活性，我们重点关注应激诱导的 NAD(P)H 脱水酶 YKL151C 及其下游邻居代谢酶 GPM1。之前的研究表明这些基因之间的区域参与了 GPM1 表达的调节。我们的突变实验确定了其在丰富培养基中的功能，作为远端起始 YKL151C 有义 RNA 的顺式阻遏物，以及近端起始 YKL151C 反义 RNA 的激活剂。所有三个转录本的野生型表达都需要转录因子 Gcr2。因此，在这个基因座上，基因间区域作为调节输入的焦点，驱动反义表达并介导 YKL151C 和 GPM1 的协调调节。总之，我们的研究结果表明转录因子参与了专门针对相反条件的邻近基因的联合控制以及它们之间表达的反义转录本。
Genes encoded close to one another on the chromosome are often coexpressed, by a mechanism and regulatory logic that remain poorly understood. We surveyed the yeast genome for tandem gene pairs oriented tail-to-head at which expression antisense to the upstream gene was conserved across species. The intergenic region at most such tandem pairs is a bidirectional promoter, shared by the downstream gene mRNA and the upstream antisense transcript. Genomic analyses of these intergenic loci revealed distinctive patterns of transcription factor regulation. Mutation of a given transcription factor verified its role as a regulator in trans of tandem gene pair loci, including the proximally initiating upstream antisense transcript and downstream mRNA and the distally initiating upstream mRNA. To investigate cis-regulatory activity at such a locus, we focused on the stress-induced NAD(P)H dehydratase YKL151C and its downstream neighbor, the metabolic enzyme GPM1. Previous work has implicated the region between these genes in regulation of GPM1 expression; our mutation experiments established its function in rich medium as a repressor in cis of the distally initiating YKL151C sense RNA, and an activator of the proximally initiating YKL151C antisense RNA. Wild-type expression of all three transcripts required the transcription factor Gcr2. Thus, at this locus, the intergenic region serves as a focal point of regulatory input, driving antisense expression and mediating the coordinated regulation of YKL151C and GPM1. Together, our findings implicate transcription factors in the joint control of neighboring genes specialized to opposing conditions and the antisense transcripts expressed between them.