Cross-regulation of post-translational protein modifications and effects on the histone H3 tail conformations/dynamics: A structural and mechanistic study on whole nucleosomes by Nuclear Magnetic Resonance (NMR) spectroscopy.

翻译后蛋白质修饰的交叉调节以及对组蛋白 H3 尾部构象/动力学的影响：通过核磁共振 (NMR) 光谱对整个核小体进行结构和机制研究。

• 批准号: 247285007
• 负责人: Dr. Stamatios Liokatis, Ph.D.
• 金额: --
• 依托单位: Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/247285007?language=en
• 关键词: Cross; regulation; post; translational; protein

The aim of this study is to expand my ongoing investigation on characterizing the structural and dynamic properties of histone H3 tail and its post-translational modifications (PTMs) to a system that resembles the natural occurring chromatin fiber under different functional/condensed states. Specifically, isotope-labeled histone H3 containing distinct sets of PTMs will be used to reconstitute nucleosomal arrays that will undergo folding transitions and they will be analyzed by NMR spectroscopy. Results from these analyses will advance our understanding on the role of histone tail dynamics and their PTMs on regulating transitions between functional chromatin states Additionally, differentially isotope-labeled histones will be incorporated on nucleosomes as to investigate the interplay between the catalytic and the acetyl-lysine recognition domain of the transcriptional co-activator CBP on the regulation of its acetyltransferase activity. Understanding the molecular mechanism that controls CBP activity has implications for pharmacological targeting.

本研究的目的是扩展我正在进行的研究，表征组蛋白H3尾及其翻译后修饰（PTM）的结构和动力学特性的系统，类似于不同功能/凝聚态下的天然染色质纤维。具体而言，同位素标记的组蛋白H3含有不同的PTM组将用于重构将经历折叠转变的核小体阵列，并将通过NMR光谱分析。这些分析的结果将促进我们对组蛋白尾部动力学及其PTM在调节功能染色质状态之间转换中的作用的理解 此外，将差异同位素标记的组蛋白掺入核小体，以研究转录共激活因子CBP的催化和乙酰赖氨酸识别结构域对其乙酰转移酶活性的调节之间的相互作用。了解控制CBP活性的分子机制对药理学靶向具有重要意义。

项目成果

Differentially Isotope-Labeled Nucleosomes To Study Asymmetric Histone Modification Crosstalk by Time-Resolved NMR Spectroscopy.

• DOI: 10.1002/anie.201601938
• 发表时间: 2016-07-11
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Liokatis S;Klingberg R;Tan S;Schwarzer D
• 通讯作者: Schwarzer D

Reconstitution of Nucleosomes with Differentially Isotope-labeled Sister Histones.

用差异同位素标记的姐妹组蛋白重建核小体

• DOI: 10.3791/55349
• 发表时间: 2017
• 期刊: Journal of visualized experiments : JoVE
• 作者: Liokatis