Interaction of the HAT complex SAS-I with chromatin assembly factors in S. cerevisiae

染色质复制不仅需要复制DNA序列，还需要复制染色质结构。最重要的是，组蛋白修饰模式需要在新复制的染色质上重新建立，因为它们在确定染色质是活性(常染色质)还是非活性(异染色质)方面起着至关重要的作用，这是通过控制其他因子与染色质的结合来实现的。在这项提案中，我们将把在酿酒酵母中重建常染色质乙酰化标记的模型，即H4 K16的乙酰化，进行关键测试。全球H4 K16乙酰化由SAS-I组蛋白乙酰转移酶复合体执行。基于我们的发现，SAS-I与染色质组装因子相互作用，我们将检验这样的假设，即它们将SAS-I的活性引导到特定的基因组区域。此外，我们将确定SAS-I乙酰化是在组蛋白沉积之前还是之后发生，并将从分子上剖析SAS-I与染色质组装因子之间的相互作用。最后，我们将绘制全基因组SAS-I依赖乙酰化的图表。这些研究将为细胞如何确保后代与亲代细胞在表观遗传上相同提供重要的机制见解。

Chromatin duplication entails not only copying of the DNA sequence, but also duplicating the chromatin structure. Foremost, histone modification patterns need to be reestablished on the freshly replicated chromatin, since they play a crucial role in determining whether the chromatin is active (euchromatin) or inactive (heterochromatin), which they achieve by controlling the binding of other factors to chromatin. In this proposal, we will submit models for the reestablishment of a euchromatic acetylation mark in S. cerevisiae, the acetylation of H4 K16, to critical tests. Global H4 K16 acetylation is performed by the SAS-I histone acetyltransferase complex. Based on our finding that SAS-I interacts with chromatin assembly factors, we will test the hypothesis that they direct the SAS-I activity to certain genomic regions. Furthermore, we will determine whether SAS-I acetylation occurs before or after histone deposition, and we will molecularly dissect the interaction between SAS-I and the chromatin assembly factors. Finally, we will chart genome-wide SAS-I dependent acetylation. These studies will give important mechanistic insights into how cells ensure that the offspring is epigenetically identical to the parental cells.