RECOGNITION EVENTS IN THE HISTONE/EPIGENETICS CODE

组蛋白/表观遗传学密码中的识别事件

• 批准号: 7721242
• 负责人: DINSHAW J PATEL
• 金额: $ 1.53万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-15 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721242
• 关键词: Acetylation; Binding; Bromodomain; Chromatin; Code; Complex; Computer Retrieval of Information on Scientific Projects Database; Epigenetic Process; Event; Funding; Grant; Histone H3; Histones; Individual; Institution; Link; Lysine; Mediating; Methylation; Modification; Mono-S; PHD Finger; Phosphorylation; Play; Polycomb; Post-Translational Protein Processing; Process; Protein Binding; Proteins; Range; Recruitment Activity; Reporting; Research; Research Personnel; Resources; Role; Signal Transduction; Source; Staging; Transcriptional Activation; Transcriptional Regulation; Translating; United States National Institutes of Health; histone methyltransferase; peptide structure

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Post-translational modification of histones by phosphorylation, acetylation, and methylation plays a key role in transcriptional regulation, but also directs other cellular DNA-mediated processes. Histone modifications can act as signaling marks, recruiting specific protein-binding modules. These mediate functional readout and translate distinct histone modification states into biologically meaningful function. For example, bromodomain-containing proteins, such as pCAF, GCN5, and TAF250, have been shown to bind to several acetyl-lysine residues in core histones H3 and H4, thereby mediating transcriptional activation. Furthermore, the chromodomain proteins HP1 and Polycomb (Pc), have been implicated in the recognition of individual methylated lysine residues, namely H3-lysine 9 and H3-lysine 27, thereby mediating the formation of silenced states of chromatin. The modification of histone lysine residues by methylation has enormous signaling potential, as lysines can be mono-, di-, or tri-methylated. These different modification stages are directed by different histone methyltransferases and are targeted to distinct domains of chromatin. We report below on structures of peptide-protein complexes that define state-specific recognition of methylated K4 on H3 by WDR5, a WD40 module and the PHD finger of BPTF. Trimethylation of K4 on H3 has been linked to transcriptional activation in a range of eukaryotic species.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 通过磷酸化，乙酰化和甲基化对组蛋白的翻译后修饰在转录调节中起关键作用，但也指导其他细胞DNA介导的过程。组蛋白的修饰可以充当信号标记，募集特定的蛋白质结合模块。这些介导功能读数并将不同的组蛋白修饰态转化为生物学上有意义的功能。例如，已显示含溴脱域的蛋白（例如PCAF，GCN5和TAF250）与核心组蛋白H3和H4中的几个乙酰基赖氨酸残基结合，从而介导转录激活。此外，染色体蛋白蛋白HP1和PolyComb（PC）与识别单个甲基化赖氨酸残基的识别有关，即H3-赖氨酸9和H3-赖氨酸27，从而介导了沉默的染色质状态。 通过甲基化对组蛋白赖氨酸残基的修饰具有巨大的信号传导潜力，因为赖氨酸可以是单，二甲基或三甲基化的。这些不同的修饰阶段由不同的组蛋白甲基转移酶指导，并针对染色质的不同结构域。 我们下面报告了肽蛋白复合物的结构，这些结构定义了WDR5，WD40模块和BPTF的PHD指的H3对H3上的甲基化K4的识别。 H3上K4的三甲基化与一系列真核物种中的转录激活有关。