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

• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2014 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 109546710

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.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 81: Chromatin Changes in Differentiation and Malignancies
• Applicant Institution: Philipps-Universität Marburg
• Project Head: Professor Dr. Tilman Borggrefe