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A12 - Tilman Borggrefe:

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

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.

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