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

RBP-J/SHARP 辅阻遏物复合物介导的染色质调节 (A12)

• 批准号: 261132446
• 金额: --
• 依托单位: Biochemisches Institut
• 依托单位国家: 德国
• 项目类别: CRC/Transregios
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/261132446?language=en
• 关键词: Chromatin; regulation; mediated; RBP; SHARP

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.

Notch通路是一种高度保守的细胞间信号传导机制，最终导致基因表达的变化。在不存在Notch信号的情况下，转录因子RBPJ与其辅因子SHARP一起通过募集NCoR/HDAC复合物来主动抑制Notch靶基因。基于RBPJ/SHARP复合物的晶体结构和CRISPR/Cas9介导的敲除，我们将利用全基因组方法分析基于抑制性染色质的机制。此外，我们将筛选破坏SHARP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。