The genome-wide architecture of chromatin-associated proteins that maintains chromosome integrity and gene regulation is not well defined. Here we use chromatin immunoprecipitation, exonuclease digestion and DNA sequencing (ChIP–exo/seq)^1,2 to define this architecture in Saccharomyces cerevisiae. We identify 21 meta-assemblages consisting of roughly 400 different proteins that are related to DNA replication, centromeres, subtelomeres, transposons and transcription by RNA polymerase (Pol) I, II and III. Replication proteins engulf a nucleosome, centromeres lack a nucleosome, and repressive proteins encompass three nucleosomes at subtelomeric X-elements. We find that most promoters associated with Pol II evolved to lack a regulatory region, having only a core promoter. These constitutive promoters comprise a short nucleosome-free region (NFR) adjacent to a +1 nucleosome, which together bind the transcription-initiation factor TFIID to form a preinitiation complex. Positioned insulators protect core promoters from upstream events. A small fraction of promoters evolved an architecture for inducibility, whereby sequence-specific transcription factors (ssTFs) create a nucleosome-depleted region (NDR) that is distinct from an NFR. We describe structural interactions among ssTFs, their cognate cofactors and the genome. These interactions include the nucleosomal and transcriptional regulators RPD3-L, SAGA, NuA4, Tup1, Mediator and SWI–SNF. Surprisingly, we do not detect interactions between ssTFs and TFIID, suggesting that such interactions do not stably occur. Our model for gene induction involves ssTFs, cofactors and general factors such as TBP and TFIIB, but not TFIID. By contrast, constitutive transcription involves TFIID but not ssTFs engaged with their cofactors. From this, we define a highly integrated network of gene regulation by ssTFs.

维持染色体完整性和基因调控的染色质相关蛋白的全基因组结构尚未明确定义。在这里，我们使用染色质免疫沉淀、核酸外切酶消化和 DNA 测序 (ChIP–exo/seq) ^1,2来定义酿酒酵母中的这种结构。我们鉴定了 21 个元组合，由大约 400 种不同的蛋白质组成，这些蛋白质与 DNA 复制、着丝粒、亚端粒、转座子和 RNA 聚合酶 (Pol) I、II 和 III 的转录相关。复制蛋白吞噬核小体，着丝粒缺乏核小体，抑制蛋白在亚端粒 X 元件处包含三个核小体。我们发现大多数与 Pol II 相关的启动子进化为缺乏调控区，只有一个核心启动子。这些组成型启动子包含与 +1 核小体相邻的短无核小体区域 (NFR)，它们一起结合转录起始因子 TFIID 形成预起始复合物。定位的绝缘体保护核心启动子免受上游事件的影响。一小部分启动子进化出了一种诱导性结构，其中序列特异性转录因子 (ssTF) 创建了一个与 NFR 不同的核小体耗尽区 (NDR)。我们描述了 ssTF、它们的同源辅因子和基因组之间的结构相互作用。这些相互作用包括核小体和转录调节因子 RPD3-L、SAGA、NuA4、Tup1、Mediator 和 SWI-SNF。令人惊讶的是，我们没有检测到 ssTF 和 TFIID 之间的相互作用，这表明这种相互作用并不稳定发生。我们的基因诱导模型涉及 ssTF、辅因子和一般因子，例如 TBP 和 TFIIB，但不包括 TFIID。 相比之下，组成型转录涉及 TFIID，但不涉及与其辅因子结合的 ssTF。由此，我们定义了 ssTF 高度集成的基因调控网络。