Reestablishment of epigenetic patterns of histone modification after DNA replication and chromatin assembly in S. cerevisiae

真核生物细胞核中的DNA被包装成一种复杂的核蛋白结构，称为染色质。根据基因组中单个区域的功能，染色质的组蛋白成分携带不同类型的翻译后修饰（表观遗传），这些修饰决定了其他蛋白质与染色质结合并调节其功能的能力。这就提出了一个问题，当细胞分裂时这种结构是如何复制的。复制不仅需要复制原始DNA序列，还需要将其压缩成染色质以及表观遗传印记。在本项目中，我们将以酿酒酵母为模式生物，研究DNA复制和染色质组装过程中表观遗传修饰的命运。我们将确定哪些修饰模式与组蛋白沉积相关，修饰模式在复制后调整到原始模式的速度有多快，以及染色质组装因子是否参与这一过程。此外，我们将研究修饰的局部差异的建立是否与DNA复制和染色质组装耦合，或者它们是否独立形成。这一信息对于理解后代在遗传和表观遗传上如何与父母相同至关重要。表观遗传程序的紊乱可导致细胞表达的失调，从而引起疾病。

DNA in the eukaryotic nucleus is packaged into a complex nucleoprotein structure called chromatin. Depending on the function of individual regions in the genome, the histone components of the chromatin carry different types of posttranslational (epigenetic) modifications that dictate the ability of other proteins to bind to chromatin and modulate its function. This raises the question how this structure is duplicated when cells divide. The duplication entails copying not only the primary DNA sequence, but also the compaction into chromatin as well as the epigenetic imprints. In this project, we will investigate the fate of epigenetic modifications during DNA replication and chromatin assembly using the yeast S. cerevisiae as a model organism. We will determine which modification patterns correlate with histone deposition, how soon modification patterns are adjusted to the original pattern after replication, and whether chromatin assembly factors are involved in this process. Furthermore, we will investigate whether the establishment of local differences in modification is coupled to DNA replication and chromatin assembly, or whether they are formed independently. This information will be crucial to understand how the offspring is genetically as well as epigenetically identical to the parent. Disturbance of epigenetic programming can lead to the disregulation of cellular expression and thus can cause disease.