DEPHOSPHORYLATION REGULATION OF TRANSCRIPTION BY CTD PHOSPHATASES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 RNA聚合酶II的C末端结构域通过其磷酸化状态募集RNA调节蛋白，从而调控基因转录过程。因此，CTD磷酸酶，如人SCP磷酸酶，可以主宰细胞的表观遗传命运。我们在实验中使用的晶体是CTD磷酸酶人Scp1的复杂结构，从其底物-RNA聚合酶II的C-末端结构域结合到磷酸化的多肽上，具有不同的磷酸化状态。此外，我们还发现了SCP磷酸酶的新型抑制剂，并寻求获得蛋白质-抑制剂复合体的结构。此类抑制物可用于指导神经干细胞分化。

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. The regulation of gene transcription process is tightly controlled by the temporal and spatial recruitment of RNA regulatory proteins by the C- terminal domain of RNA polymerase II through its phosphorylation states. Therefore, CTD phosphatases such as human Scp phosphatases can dominate the epigenetic fate of the cell. The crystals we used in this experiments are the complex structures of CTD phosphatases human Scp1 bound to phosphorylated peptides from its substrate, the C-terminal domain of RNA polymerase II with different registration of phosphorylation state. Furthermore, we identified novel inhibitors for Scp phosphatases and seek to obtain structures for protein-inhibitor complex. Such inhibitors can be used to direct neuronal stem cell differentiation.