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

NSD 组蛋白甲基转移酶家族假定组蛋白读取器功能的分子机制研究。

• 批准号: 191607619
• 负责人: Dr. Robert Liefke
• 金额: --
• 依托单位: Institut für Molekularbiologie und Tumorforschung (IMT)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/191607619?language=en
• 关键词: Investigation; molecular; mechanism; putative; histone

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.

组蛋白翻译后修饰和组蛋白密码子的结合参与了基因表达的调控。到目前为止，人们还很难理解组蛋白密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读取组蛋白修饰的结构域（组蛋白阅读器结构域）的蛋白质相比，NSD蛋白家族具有六个组蛋白阅读器结构域的独特紧凑簇。该簇内多个位置的单点突变导致功能障碍的酶，表明该簇作为一个单元发挥作用，其中每个单域是不可或缺的。我建议研究这个专门单位的假定组蛋白阅读器功能，以深入了解某些组蛋白代码是如何通过几个组蛋白阅读器域的联合作用来读取的机制。了解这种原型组蛋白阅读器的机制可能会提高创建定制组蛋白阅读器的可能性，识别其他组蛋白修饰组合。这些人工组蛋白阅读器可以成为研究和医学中有价值的多功能工具。