Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, France.
Université Paris Cité, CNRS, Institut Jacques Monod, 75013 Paris, France.
Cell Rep. 2023 May 30;42(5):112465. doi: 10.1016/j.celrep.2023.112465. Epub 2023 May 2.
Chromatin organization is crucial for transcriptional regulation in eukaryotes. Mediator is an essential and conserved co-activator thought to act in concert with chromatin regulators. However, it remains largely unknown how their functions are coordinated. Here, we provide evidence in the yeast Saccharomyces cerevisiae that Mediator establishes physical contact with RSC (Remodels the Structure of Chromatin), a conserved and essential chromatin remodeling complex that is crucial for nucleosome-depleted region (NDR) formation. We determine the role of Mediator-RSC interaction in their chromatin binding, nucleosome occupancy, and transcription on a genomic scale. Mediator and RSC co-localize on wide NDRs of promoter regions, and specific Mediator mutations affect nucleosome eviction and TSS-associated +1 nucleosome stability. This work shows that Mediator contributes to RSC remodeling function to shape NDRs and maintain chromatin organization on promoter regions. It will help in our understanding of transcriptional regulation in the chromatin context relevant for severe diseases.
染色质组织对于真核生物的转录调控至关重要。中介体是一种必不可少且保守的共激活因子，被认为与染色质调节剂协同作用。然而，它们的功能如何协调在很大程度上仍然未知。在这里，我们在酵母酿酒酵母中提供了证据，表明中介体与 RSC（重塑染色质结构）建立物理接触，RSC 是一种保守且必需的染色质重塑复合物，对于核小体缺失区域 (NDR) 的形成至关重要。我们确定了 Mediator-RSC 相互作用在其染色质结合、核小体占有率和全基因组转录中的作用。中介体和 RSC 在启动子区域的广泛 NDR 上共定位，并且特定的 Mediator 突变会影响核小体驱逐和 TSS 相关的+1 核小体稳定性。这项工作表明，中介体有助于 RSC 重塑功能，塑造 NDR 并维持启动子区域的染色质组织。它将有助于我们理解与严重疾病相关的染色质背景下的转录调控。
