Nora Jahnen
Chromatin Remodeling and Epigenetics in Ageing 

I am a trained biologist with experience in structural biology and neurobiology, now pursuing my interest in epigenetics at the AG Längst (BCIII department). My project focuses on BAZ2A, a chromatin remodeling factor and part of the nucleolar remodeling complex (NoRC), an epigenetic regulator of gene expression. NoRC is well-studied for its role in silencing rRNA genes in the nucleolus. Crucial for its function and genomic targeting is the interaction between the RNA-binding domain (TAM domain) of BAZ2A and a stem-loop-structured RNA called pRNA. This RNA binding is essential for the activation of NoRC and its localization to nucleoli. Upon RNA binding NoRC can interact with chromatin and recruits chromatin-modifying enzymes (DNMTs, HDACs) resulting in heterochromatin formation and therefore silencing of rDNA.

 

Since RNA binding by BAZ2A is crucial for its role in mediating gene expression changes, we hypothesize that the TAM domain is a potential drug target. Using fluorescence polarization, we performed an inhibitor screen and identified 13 compounds that effectively inhibit the TAM-pRNA interaction. Interestingly, these compounds all belong to a substance class known for antioxidative, anti-inflammatory, and partially senolytic properties.

 

Based on this finding, we are investigating the role of BAZ2A and the closely related BAZ2B protein in cellular senescence. For this, we use a senescence model in IMR90 cells, where senescence is chemically induced using a small molecule called inflachromene. Our aim is to determine whether the inhibitors we identified can slow down senescence onset or even reverse senescence, shedding light on the role of chromatin remodeling in this process.

 

Contact - Nora.Jahnen@ur.de

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