RECOGNITION EVENTS IN THE HISTONE/EPIGENETICS CODE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 通过磷酸化、乙酰化和甲基化对组蛋白进行的翻译后修饰在转录调控中起关键作用，但也指导其他细胞DNA介导的过程。组蛋白修饰可以作为信号标记，招募特定的蛋白质结合模块。这些介导功能读出并将不同的组蛋白修饰状态转化为生物学上有意义的功能。例如，含溴结构域的蛋白质，如pCAF、GCN 5和TAF 250，已显示与核心组蛋白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，染色体结构域蛋白HP 1和Polycomb（Pc）涉及单个甲基化赖氨酸残基的识别，即H3-赖氨酸9和H3-赖氨酸27，从而介导染色质沉默状态的形成。 组蛋白赖氨酸残基的甲基化修饰具有巨大的信号传导潜力，因为赖氨酸可以被单甲基化、二甲基化或三甲基化。这些不同的修饰阶段由不同的组蛋白甲基转移酶指导，并靶向染色质的不同结构域。 我们在下面报告了肽-蛋白质复合物的结构，该复合物定义了WDR 5、WD 40模块和BPTF的PHD指对H3上甲基化K4的状态特异性识别。在一系列真核生物中，H3上K4的三甲基化与转录激活有关。

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.