Acetylation of lysine 16 on histone H4 as a dynamic epigenetic mark during transcription and replication (A07*)

本项目的目的是获得机制的见解H4 K16乙酰化的动态沉积的SAS-I组蛋白乙酰转移酶复合物在酵母基因组中。H4 K16 Ac的分布下调SAS-I的时间和空间调控将在全基因组水平上进行测量，这将使我们能够模拟这种表观遗传标记的转录和复制偶联遗传，我们将研究这如何依赖于组蛋白伴侣。H4 K16 Ac的这些体内研究将通过SAS-I复合物的生物化学/结构研究来补充。总而言之，这将使我们能够揭示H4 K16乙酰化功能模块内表观遗传的基本原理，这对于理解真核基因组内基因表达功能域的建立非常重要。

The aim of this project is to obtain mechanistic insights into the dynamic deposition of H4 K16 acetylation by the SAS-I histone acetyltransferase complex in the yeast genome. The temporal and spatial regulation of H4 K16Ac distribution upon downregulation of SAS-I will be measured on a genome-wide level, which will allow us to model transcription- and replication-coupled inheritance of this epigenetic mark, and we will study how this depends on histone chaperones. These in vivo studies of H4 K16Ac will be complemented by biochemical/ structural studies of the SAS-I complex. Altogether, this will allow us to uncover the basic principles of epigenetic inheritance within the functional module of H4 K16 acetylation, which is important in order to understand the establishment of functional domains of gene expression within the eukaryotic genome.