The function of YEATS domain proteins in S. cerevisiae

在真核生物中，DNA被包装成由DNA、组蛋白和非组蛋白组成的核蛋白结构。DNA在染色质中的堆积对于基因表达的调控和染色体的稳定性是非常重要的。染色质结构可以通过对组蛋白添加翻译后修饰来调节，包括乙酰化、甲基化、磷酸化和泛素化。然而，尽管进行了几十年的研究，但对这些组蛋白修饰的功能后果知之甚少。目前公认的假说是，组蛋白翻译后修饰起到了“灯塔”的作用，招募了改变染色质结构的“效应器”蛋白。然而，到目前为止，这些效应蛋白中还很少被鉴定出来。我们最近在Yaf9p中检测到染色质结合活性，Yaf9p是一种含有Yaf9-en1-AF9-Taf14-Sas5结构域的蛋白质。含有Yeats结构域的蛋白质是多个染色质修饰复合体的组成部分，我们有兴趣确定这些蛋白质是否特异性地识别翻译后修饰的组蛋白。结合遗传学和生物化学方法，我们将在模式生物酿酒酵母中表征叶芝结构域蛋白与染色质的相互作用。确定这些蛋白质的功能将使我们能够理解组蛋白修饰如何调节染色质结构。

In eukaryotes DNA is packaged into a nucleoprotein structure consisting of DNA, histones, and non-histone proteins. The packing of DNA into chromatin is important for the regulation of gene expression and for chromosome stability. Chromatin structure can be regulated by the addition of post-translational modifications to histones, including acetylation, methylation, phosphorylation, and ubiquitination. However, despite several decades of study, little is known regarding the functional consequences of these histone modifications. The current accepted hypothesis is that histone post-translational modifications serve as "beacons" to recruit "effector" proteins that modify chromatin structure. However, to date, few of these effector proteins have been identified. We have recently detected chromatin-binding activity in Yaf9p, a YEATS (Yaf9-ENL-AF9-Taf14-Sas5) domain-containing protein. Proteins containing YEATS domains are components of multiple chromatin modifying complexes, and we are interested in determining whether these proteins specifically recognize post-translationally modified histones. Using a combination of genetic and biochemical approaches we will characterize the interaction of the YEATS-domain proteins with chromatin in the model organism, Saccharomyces cerevisiae. Determining the function of these proteins will enable us to understand how histone modifications can regulate chromatin structure.