Investigation of the molecular mechanism of the putative histone reader function of the NSD histone methyltransferase family.

组蛋白的翻译后修饰的组合，组蛋白密码已被认为与基因表达的调节有关。到目前为止，人们很难理解组蛋白代码是如何被读取并翻译成下游事件的。与许多其他具有能够阅读组蛋白修饰结构域(组蛋白阅读器结构域)的蛋白质不同，NSD蛋白家族有一个独特的由六个组蛋白阅读器结构域组成的紧凑簇。该簇中多个位置的单点突变会导致一种功能失调的酶，这表明该簇作为一个单位发挥作用，其中每个单一结构域都是不可或缺的。我建议研究这个特殊单位的组蛋白阅读器功能，以深入了解某个组蛋白密码是如何通过几个组蛋白阅读器结构域的联合作用来阅读的。了解这种典型的组蛋白阅读器的机制可能会提高创建定制的组蛋白阅读器的可能性，从而识别其他组蛋白修饰组合。这些人造组蛋白阅读器可能会成为研究和医学中有价值的多功能工具。

The combination of posttranslational modifications of histones the histone code has been implicated in the regulation of gene expression. So far it is hardly understood how the histone code is read and translated into downstream events. In contrast to many other proteins with domains able to read histone modifications (histone reader domains), the NSD protein family has a unique compact cluster of six histone reader domains. Single point mutations at multiple positions within this cluster leads to a dysfunctional enzyme, indicating that this cluster functions as a unit, where each single domain is indispensable. I propose to study the putative histone reader function of this specialized unit, to gain insights into the mechanism how a certain histone code is read by the combined action of several histone reader domains. Understanding the mechanisms of such a prototypic histone reader might raise the possibility to create customized histone readers, recognizing other histone modification combinations. These artificial histone readers could become valuable and versatile tools in research and medicine.