Epigenetic principles and mechanisms underlying nervous system functions in health and disease

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

Epigenetics and epigenomic medicine encompass a new science of brain and behavior that are already providing unique insights into the mechanisms underlying brain development, evolution, neuronal and network plasticity and homeostasis, senescence, the etiology of diverse neurological diseases and neural regenerative processes. Epigenetic mechanisms include DNA methylation, histone modifications, nucleosome repositioning, higher order chromatin remodeling, non-coding RNAs, and RNA and DNA editing. RNA is centrally involved in directing these processes, implying that the transcriptional state of the cell is the primary determinant of epigenetic memory. This transcriptional state can be modified not only by internal and external cues affecting gene expression and post-transcriptional processing, but also by RNA and DNA editing through activity-dependent intracellular transport and modulation of RNAs and RNA regulatory supercomplexes, and through trans-neuronal and systemic trafficking of functional RNA subclasses. These integrated processes promote dynamic reorganization of nuclear architecture and the genomic landscape to modulate functional gene and neural networks with complex temporal and spatial trajectories. Epigenetics represents the long sought after molecular interface mediating gene-environmental interactions during critical periods throughout the lifecycle. The discipline of environmental epigenomics has begun to identify combinatorial profiles of environmental stressors modulating the latency, initiation and progression of specific neurological disorders, and more selective disease biomarkers and graded molecular responses to emerging therapeutic interventions. Pharmacoepigenomic therapies will promote accelerated recovery of impaired and seemingly irrevocably lost cognitive, behavioral, sensorimotor functions through epigenetic reprogramming of endogenous regional neural stem cell fate decisions, targeted tissue remodeling and restoration of neural network integrity, plasticity and connectivity.

Original languageEnglish (US)
Pages (from-to)305-341
Number of pages37
JournalProgress in Neurobiology
Volume86
Issue number4
DOIs
StatePublished - Dec 11 2008

Fingerprint

Epigenomics
Nervous System
Health
RNA Editing
RNA
Histone Code
RNA Transport
Untranslated RNA
Neuronal Plasticity
Chromatin Assembly and Disassembly
Neural Stem Cells
Nucleosomes
Gene Regulatory Networks
DNA
Brain
DNA Methylation
Nervous System Diseases
Cues
Homeostasis
Biomarkers

Keywords

  • Cerebrovascular disorders
  • Chromatin remodeling
  • Environmental epigenomics
  • Epigenetics
  • Learning and memory
  • Neurodegenerative diseases
  • Neurodevelopmental disorders
  • Neuroimmunology
  • Neurooncology
  • Neuropsychiatric diseases
  • Non-coding RNAs
  • Nuclear architecture
  • Pharmacoepigenomics
  • RNA and DNA editing
  • RNA regulatory networks
  • Stem cell biology

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Epigenetic principles and mechanisms underlying nervous system functions in health and disease. / Mehler, Mark F.

In: Progress in Neurobiology, Vol. 86, No. 4, 11.12.2008, p. 305-341.

Research output: Contribution to journalArticle

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