Chromatin regulation mediated by the RBP-J/SHARP corepressor complex (A12)

Notch通路是一种高度保守的细胞间信号传递机制，最终导致基因表达的变化。在没有Notch信号的情况下，转录因子RBPJ及其辅助因子Sharp通过招募NCoR/HDAC-复合体来主动抑制Notch靶基因。基于RBPJ/Sharp-Complex和CRISPR/Cas9介导的基因敲除的晶体结构，我们将利用全基因组方法分析基于染色质的抑制机制。此外，我们将筛选破坏尖锐抑制功能的小分子。该项目可能有助于发现Notch相关疾病的新治疗靶点。

The Notch pathway is a highly conserved cell-to-cell signaling mechanism that ultimately results in changes in gene expression. In the absence of a Notch signal, the transcription factor RBPJ together with its cofactor SHARP actively represses Notch target genes by recruiting the NCoR/HDAC-complex. Based on the crystal structure of the RBPJ/SHARP-complex and CRISPR/Cas9-mediated knockouts we will analyze the repressive chromatin-based mechanism utilizing genomewide approaches. Furthermore, we will screen for small-molecules that disrupt the SHARP-repressive function. The project may help to discover novel therapeutic targets for Notch-associated diseases.