Repression by the Arabidopsis TOPLESS corepressor requires association with the core Mediator complex

背景+问题：The plant corepressor TOPLESS (TPL) is recruited to a large number of loci that are selectively induced in response to developmental or environmental cues, yet the mechanisms by which it inhibits expression in the absence of these stimuli is poorly understood. 

研究基础：Previously, we had used the N-terminus of Arabidopsis thaliana TPL to enable repression of a synthetic auxin response circuit in Saccharomyces cerevisiae (yeast). 

主要研究：Here, we leveraged the yeast system to interrogate the relationship between TPL structure and function, specifically scanning for repression domains.

结果1：We identified a potent repression domain in Helix 8 located within the CRA domain, which directly interacted with the Mediator middle module subunits Med21 and Med10. 

结果2：Interactions between TPL and Mediator were required to fully repress transcription in both yeast and plants. 

结果3：In contrast, we found that multimer formation, a conserved feature of many corepressors, had minimal influence on the repression strength of TPL.

 摘 要 

植物共抑制因子TPL被招募到很多基因座上，这些基因座会被选择性地诱导以响应发育或环境信号，然而在没有这些刺激的情况下，TPL抑制表达的机制却不清楚。先前，作者利用拟南芥TPL的N端抑制酵母中的一个人工合成的生长素响应回路。本文中，作者利用酵母系统来研究TPL结构和功能之间的关系，特别是扫描抑制结构域。作者在位于CRA结构域内的Helix 8中发现了一个有效的抑制结构域，其能够直接与Med21和Med10互作。在酵母和植物中，TPL和Mediator之间的互作是完全抑制转录所必需的。相反，作者发现许多共抑制因子的保守特征，即多聚体的形成，对TPL的抑制强度影响很小。