Activity-Dependent Chromatin Regulation and 3D Genome Architecture in the Nervous System

Recent advances in genomics, genome editing, and imaging technologies have revealed that neural activity can rapidly alter chromatin accessibility, reposition genomic loci within the nucleus, and reorganize long-range chromosomal interactions. The 3D genome refers to the spatial organization of DNA within the cell nucleus, encompassing how chromosomes fold, how distant regulatory elements such as enhancers and promoters come into physical contact, and how genomic regions are positioned within nuclear compartments. This spatial organization is increasingly recognized as a critical layer of gene regulation. These processes are increasingly understood to be cell-type specific and developmentally regulated, operating across neurons, glia, and neural progenitor populations. Importantly, signalling-chromatin interfaces appear to be redeployed during regeneration and repair, linking activity-dependent genome regulation to neuronal survival, neurogenesis, and tissue remodeling following injury.Disruption of signalling-driven chromatin regulation and 3D genome architecture has been implicated across the lifespan of the nervous system, from neurodevelopmental disorders to brain ageing and age-related conditions, including neurodegenerative diseases such as ALS and Alzheimer’s disease, as well as brain tumors, stroke, and sensory system degeneration. A growing body of work now highlights that chromatin remodeling, epigenetic drift, heterochromatin reorganization, and altered 3D genome topology are core features of brain ageing, and that these changes both intersect with and extend beyond classical neurodegenerative pathology. Mutations in chromatin regulators, altered enhancer landscapes, dysregulated cell cycle signalling, and defects in genome topology can uncouple neural activity from appropriate transcriptional responses, resulting in impaired plasticity, aberrant cell fate decisions, and disease progression. Understanding how intracellular signalling pathways converge on chromatin and nuclear architecture across development, ageing, and disease therefore represents a critical frontier in molecular neuroscience, with significant implications for therapeutic intervention.This Research Topic aims to bring together studies that dissect the molecular mechanisms linking neural activity and intracellular signalling to chromatin regulation and spatial genome organization across the nervous system. By integrating signalling pathways, genome architecture, and gene regulation, this collection seeks to provide a unified framework for understanding how activity-dependent genome dynamics shape neural function in physiological, ageing, and pathological contexts.We welcome submissions deploying molecular, biochemical, genomic, imaging, electrophysiological, and computational approaches, including studies using CRISPR-based perturbations, viral gene delivery, and advanced in vitro systems such as brain and sensory organoids, alongside in vivo genetic models and human-derived tissues. Contributions that connect chromatin and genome architecture changes to defined cellular, synaptic, regenerative, or circuit-level phenotypes are particularly encouraged.Topics of interest include, but are not limited to:• Signalling pathways that couple synaptic activity, growth factors, or injury-related cues to chromatin remodeling and transcriptional control• Activity-dependent regulation of histone modifications, DNA methylation, chromatin accessibility, and enhancer dynamics• Roles of transcription factors, chromatin remodelers, epigenetic enzymes, and cell cycle regulators in neural gene expression programs• Mechanisms governing 3D genome organization, including enhancer-promoter looping, topologically associating domains, and nuclear compartmentalization in neural cells• Cell-type and developmental specificity of signalling–chromatin interactions in neurons, glia, and neural stem or progenitor cells• Chromatin and nuclear architecture changes in the ageing brain, including epigenetic drift, heterochromatin reorganization, and age-associated alterations in genome topology • Intersections between brain ageing, cellular senescence, and chromatin-mediated transcriptional dysregulation in neurons and glia• Live-cell, super-resolution, and high-content imaging of chromatin dynamics and nuclear organization in response to neural activity• Integration of multiomic approaches to link signalling cascades, chromatin state, and transcriptional output• Dysregulation of chromatin and 3D genome architecture in neurodevelopmental, neurodegenerative, neoplastic, sensory disorders, and ageing• Genetic and pharmacological modulation of chromatin regulators and signalling pathways to promote neuroprotection, regeneration, or functional recovery, including in the aging nervous system Topic editors: Koby Baranes, Jaime Imitola, MD, Zaen Zeier Source: https://www.frontiersin.org/research-topics/77514/activity-dependent-chromatin-regulation-and-3d-genome-architecture-in-the-nervous-system