Establishment of global histone acetylation patterns by the HAT complex SAS-I in S. cerevisiae

真核生物需要复杂的机制来确保基因组中的基因表达以正确的时间和空间方式进行。翻译后组蛋白修饰是控制基因表达的一种机制。其中，H4赖氨酸16（H4 K16 Ac）的乙酰化在维持常染色质同一性方面起着重要作用。在上一个授权期间，我们已经调查了全球H4 K16 Ac沉积组蛋白乙酰转移酶复合物SAS-I在酿酒酵母，这使我们确定了意想不到的作用SAS-I在转录延伸和抑制的隐蔽启动ORF内。在本提案中，我们将继续这项工作，并将定义H4 K16 Ac沉积SAS-I的机制。我们将确定它是如何连接到复制和转录依赖性和非依赖性组蛋白沉积。此外，我们将确定染色质组装因子CAF-I和Asf 1如何有助于稳态H4 K16 Ac水平，以及它们如何影响S期内外的动态SAS-I依赖性H4 K16 Ac。这些研究对于了解SAS-I乙酰化是如何针对某些基因组区域的，并对真核生物用于在其基因组内建立染色质结构域的机制提供新的见解是重要的。

Eukaryotic organisms require sophisticated mechanisms to ensure that gene expression in their ge-nome is carried out in the correct temporal and spatial manner. Posttranslational histone modifications are one mechanism by which gene expression is controlled. Among these, acetylation of H4 lysine 16 (H4 K16Ac) plays an important role in maintaining euchromatic identity. In the previous grant period, we have investigated global H4 K16Ac deposition by the histone acetyltransferase complex SAS-I in Saccharomyces cerevisiae, which lead us to identify unanticipated roles for SAS-I in transcription elongation and the suppression of cryptic initiation within ORFs. In this proposal, we will continue this work and will define the mechanism of H4 K16Ac deposition by SAS-I. We will determine how it is connected to replication- and transcription-dependent and -independent histone deposition. Furthermore, we will determine how the chromatin assembly factors CAF-I and Asf1 contribute to steady-state H4 K16Ac levels as well as how they influence dynamic SAS-I-dependent H4 K16Ac inside and outside of S-phase. These studies are important in order to learn how SAS-I acetylation is directed to certain genomic regions and provide novel insights into the mechanisms that eukaryotes use to establish chromatin domains within their genome.