Structure-system correlation identifies a gene regulatory Mediator submodule
Structure-system correlation identifies a gene regulatory Mediator submodule
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DOI：
10.1101/gad.465108
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发表时间：
2008-04-01
影响因子：
10.5
通讯作者：
Cramer, Patrick
中科院分区：
文献类型：
--
作者：
Lariviere, Laurent;Seizl, Martin;Cramer, Patrick
晶体学、生物化学和基因表达分析的结合将共激活子复合物 Med8C/18/20 确定为介体头模块的功能独特的子模块。 Med8C 形成保守的 α 螺旋，将 Med18/20 与介体连接。体内 Med8C 的缺失会导致 Med18/20 从 Mediator 解离，并导致提取物转录活性丧失。删除 med8C、med18 或 med20 会导致酵母转录组发生类似的变化，从而将 Med8C/18/20 确立为非激活基因（包括接合基因）低转录水平所需的主要阳性、基因特异性子模块。所提出的基于结构的系统扰动优于基因调控的基因缺失分析。
A combination of crystallography, biochemistry, and gene expression analysis identifies the coactivator subcomplex Med8C/18/20 as a functionally distinct submodule of the Mediator head module. Med8C forms a conserved alpha-helix that tethers Med18/20 to the Mediator. Deletion of Med8C in vivo results in dissociation of Med18/20 from Mediator and in loss of transcription activity of extracts. Deletion of med8C, med18, or med20 causes similar changes in the yeast transcriptome, establishing Med8C/18/20 as a predominantly positive, gene-specific submodule required for low transcription levels of nonactivated genes, including conjugation genes. The presented structure-based system perturbation is superior to gene deletion analysis of gene regulation.