Epigenetic and Transcriptomic Regulations in Brain Disorders

Abstract

Epigenetic and transcriptomic mechanisms are pivotal to the human brain’s complexity, adaptability, and function, regulating gene expression without altering the DNA sequence. These processes, involving DNA methylation, histone modifications, non-coding RNAs, alternative RNA splicing, and regulatory RNAs, enable the brain to respond to developmental cues, environmental factors, and neural activity, shaping neuronal identity, synaptic plasticity, and cognitive processes. Dysregulation of the epigenetic and transcriptomic mechanisms is associated with neurodevelopmental disorders such as autism spectrum disorder and Rett syndrome, psychiatric conditions like schizophrenia and major depressive disorder, and neurodegenerative diseases including Alzheimer’s, Parkinson’s, and Huntington’s. This chapter explores how epigenetic and transcriptoincludmic systems interact through feedback loops and system-level regulation to maintain neural resilience. Advanced tools, such as single-cell sequencing, spatial transcriptomics, and CRISPR-based gene editing, allow precise mapping of gene expression across specific cell types and brain regions. Multi-omics integration enhances our understanding of brain disorders, advancing diagnosis, prevention, and personalized treatment strategies. Targeting these reversible molecular changes offers significant therapeutic potential, though challenges like cellular heterogeneity, intervention timing, and clinical translation persist.