Activation domains (ADs) within transcription factors (TFs) induce gene expression by recruiting coactivators such as the Mediator complex. Coactivators lack DNA binding domains (DBDs) and are assumed to passively follow their recruiting TFs. This is supported by direct AD-coactivator interactions seen in vitro but has not yet been tested in living cells. To examine that, we targeted two Med15-recruiting ADs to a range of budding yeast promoters through fusion with different DBDs. The DBD-AD fusions localized to hundreds of genomic sites but recruited Med15 and induced transcription in only a subset of bound promoters, characterized by a fuzzy-nucleosome architecture. Direct DBD-Med15 fusions shifted DBD localization towards fuzzy-nucleosome promoters, including promoters devoid of the endogenous Mediator. We propose that Med15, and perhaps other coactivators, possess inherent promoter preference and thus actively contribute to the selection of TF-induced genes.

中文翻译：

---

重新审视共激活因子募集模型：Med15 可以选择独立于启动子结合转录因子的靶位点


转录因子 （TF） 中的激活结构域 （AD） 通过募集共激活因子（如 Mediator 复合物）来诱导基因表达。共激活因子缺乏 DNA 结合域 （DBD），并被认为被动跟随其募集 TF。这在体外观察到的直接 AD 辅激活因子相互作用得到了支持，但尚未在活细胞中进行测试。为了检查这一点，我们通过与不同的 DBD 融合，将两个 Med15 募集的 AD 靶向一系列出芽酵母启动子。DBD-AD 融合定位于数百个基因组位点，但募集了 Med15 并仅在一部分结合启动子中诱导转录，其特征是模糊核小体结构。直接 DBD-Med15 融合将 DBD 定位转向模糊核小体启动子，包括没有内源性介质的启动子。我们提出 Med15 以及其他共激活因子具有固有的启动子偏好，从而积极促进 TF 诱导基因的选择。