Involvement of the SAGA and TFIID coactivator complexes in transcriptional dysregulation caused by separation of core and tail Mediator modules (nsRNA-Seq)

Regulation of RNA polymerase II (RNAPII) transcription requires the concerted efforts of several multisubunit coactivator complexes, which interact with the RNAPII preinitiation complex (PIC) to stimulate transcription. We previously showed that separation of the Mediator core (cMed) from Mediator’s tail module results in modest overactivation of genes annotated as highly dependent on TFIID for expression. However, it is unclear if other coactivators are involved in this phenomenon. Here, we show that the overactivation of certain genes by cMed/tail separation is blunted by disruption of the SAGA complex through removal of its structural Spt20 subunit, though this downregulation does not appear to depend on reduced SAGA association with the genome. Consistent with the enrichment of TFIID-dependent genes among genes overactivated by cMed/tail separation, depletion of the essential TFIID subunit Taf13 suppressed overactivation of these genes when Med16 was simultaneously removed. As with SAGA, this effect did not appear to be dependent on reduced genomic association of TFIID.RNA聚合酶II（RNA polymerase II, RNAPII）的转录调控，需要多个多亚基辅激活因子复合物协同发挥作用，这类复合物可与RNAPII预起始复合物（preinitiation complex, PIC）结合以激活转录。我们此前的研究发现，将中介体核心（Mediator core, cMed）与中介体尾部模块分离后，那些被标注为高度依赖转录因子IID（TFIID）进行表达的基因会出现适度的过度激活现象。但目前尚不清楚是否存在其他辅激活因子参与这一过程。本研究证实，通过移除SAGA复合物的结构性亚基Spt20以破坏该复合物，可削弱cMed与尾部模块分离后部分基因的过度激活效应；不过这种下调效应似乎并不依赖于SAGA与基因组结合能力的减弱。与cMed/尾部模块分离后过度激活的基因中富集TFIID依赖基因的现象一致，当同时移除Med16时，敲除TFIID的必需亚基Taf13可抑制上述基因的过度激活。与SAGA复合物的情况类似，这一效应似乎也不依赖于TFIID与基因组结合能力的降低。