Temporal and Cell-Specific Regulation of Synaptic Homeostasis by the Chromatin Remodeler Chd1 - PubMed
5 hours ago
- #epigenetic regulation
- #epilepsy
- #autism
- Disruptions in chromatin remodelers and synaptic proteins are major genetic risk factors for autism spectrum disorder (ASD).
- CHD2, a chromatin remodeler linked to ASD, epilepsy, and intellectual disability, regulates gene expression through epigenetic mechanisms.
- In Drosophila, its homologue Chd1 regulates presynaptic homeostatic potentiation (PHP), a conserved form of synaptic plasticity.
- Chd1 functions in a temporal and cell type-specific manner: required in perineurial glia for rapid PHP induction and in motoneurons, muscle, and glia for long-term maintenance.
- Chd1 controls presynaptic calcium influx and expansion of the readily releasable vesicle pool, key features of homeostatic compensation.
- An electrophysiology-based genetic screen identified 14 Chd1-dependent genes necessary for acute PHP, including the glial-specific effector Cadherin 74A.
- Loss of Chd1 increases seizure susceptibility and disrupts motor function, mirroring phenotypes in CHD2-related neurodevelopmental disorders.
- The study connects chromatin remodeling with synaptic homeostasis and highlights glial epigenetic regulation as critical for circuit stability.