Project Details
Projekt
The role of histone-methyltransferase Setd1b in brain development
Applicant
Professor Dr. André Fischer
Subject Area
Developmental Neurobiology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 563566013
Gene expression regulation is a cornerstone of cellular identity and function. Aberrant expression, driven by genetic mutations or genome-environment interactions, contributes to various neurodevelopmental and neurodegenerative diseases. Epigenetic mechanisms, such as histone modifications, are particularly critical in mediating these effects. Our research focuses on the histone modification H3K4me3, which promotes gene activation. This mark is mediated by distinct enzymatic complexes that play vital roles in brain development and function. Mutations in the enzymes responsible for H3K4me3 modifications, such as Setd1b are associated with intellectual developmental disorders (IDDs) and adult-onset conditions like Alzheimer’s disease (AD). Notably, our studies have demonstrated the necessity of controlled H3K4me3 dynamics for neuronal identity and plasticity. Preliminary findings furthermore highlight the role of long noncoding RNAs (lncRNAs) in guiding these epigenetic complexes, either by recruiting them to specific genomic loci or acting as decoys to modulate their activity. This project aims to unravel the role of Setd1b in cortical development using human cortical organoid models and to explore how lncRNAs orchestrate neuron-specific gene expression programs. We propose two main objectives: (1) investigating the epigenetic role of Setd1b in cortical development within the context of IDDs and (2) testing the hypothesis that the lncRNA NeuID mediates the neuron-specific activity of Setd1b. These objectives will be pursued through two dedicated work packages, leveraging state-of-the-art molecular, cellular, and bioinformatics tools. Our work will advance understanding of the molecular mechanisms underpinning neurodevelopmental and neurodegenerative disorders, with implications for developing novel therapeutic strategies.
DFG Programme
Priority Programmes
