Project Details
Projekt
Investigating distinct neuronal epigenetic states organized by the nucleoporin Nup153
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 563413271
During development, neurons need to receive various inputs such as synaptic inputs to build a functional network. Upon stimulation, neurons are activated and incoming information is integrated and translated into the expression of activity-related genes (ARGs). ARGs regulate cell type-specific neuroplastic function and reorganize synaptic connectivity, therefore the tight regulation of neuronal states by ARG expression is fundamental for brain development. We recently found that Nup153, one of nuclear pore complex proteins, represses ARGs at the basal state in developing neurons. Depletion of Nup153 de-represses ARG expression without additional stimulation. Accumulating evidence indicates that nuclear pore complex proteins work as a structural hub for chromatin and epigenetic regulators. Therefore, we hypothesize that Nup153 organizes neuronal state-specific epigenetic landscapes and regulates neuronal responsiveness by tuning ARG expression. In the proposed project, by combining epigenomics and proteomics approaches, we will investigate, 1) which are the Nup153-interacting epigenetic enzymes, 2) how the neuronal epigenetic landscape is regulated by Nup153, 3) how Nup153 and its epigenetic cofactors organize epigenetic states between two different neuronal states, basal versus active. Understanding epigenetic mechanisms regulating distinct neuronal states will provide new insights in the regulation of plasticity during brain development. Nuclear pore complex proteins are also recognized as a target of neurological disorders. Therefore, the success of the proposed project will provide fundamental insights into the pathophysiological development of these disorders.
DFG Programme
Priority Programmes
