2.4 INTEGRATING EPIGENETIC AND GENETIC IN POSTMORTEM BRAIN RESEARCH

Objectives: Less than 1.5 percent of the human genome encodes protein. However, vast portions of the human genome, or approximately 40 percent, are subject to epigenetic regulation, including DNA methylation and hundreds of site- and residue-specific histone modifications, potentially associated wit...

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Published inJournal of the American Academy of Child and Adolescent Psychiatry Vol. 55; no. 10; p. S87
Main Author Akbarian, Schahram
Format Journal Article
LanguageEnglish
Published Baltimore Elsevier BV 01.10.2016
Subjects
Acetylation
Autism
Autistic children
Autopsy
Brain
Child & adolescent psychiatry
Chromatin
Chromosomes
Cognition
Cortex
Deoxyribonucleic acid
DNA
DNA methylation
Editing
Entorhinal cortex
Epigenetics
Exploration
Genetic susceptibility
Genetics
Genomes
Human development
Human Genome Project
Methylation
Neurodevelopmental disorders
Neuronal-glial interactions
Neurons
Prefrontal cortex
Psychosis
Stem cell transplantation
Stem cells
Structure-function relationships
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Summary:Objectives: Less than 1.5 percent of the human genome encodes protein. However, vast portions of the human genome, or approximately 40 percent, are subject to epigenetic regulation, including DNA methylation and hundreds of site- and residue-specific histone modifications, potentially associated with neurological function. Furthermore, there is evidence for widespread epigenomic remodeling of neurons and glia in prefrontal cortex and other brain regions during the course of pre- and postnatal human development. Methods: This presentation will discuss developmental dynamics and disease- associated alterations for multiple layers of epigenetic regulation in human cerebral cortex, including histone methylation and acetylation, histone variant exchange, and chromosomal conformations. Results: Specific examples of how epigenomic studies in neurons and glia mechanistically illuminate the genetic risk architecture of autism and psychosis spectrum disorders, including monogenic neurodevelopmental disease associated with mutations in chromatin regulators, will be provided. Conclusions: Exploration of chromatin structure and function in developing and diseased human brain, and in cultured cells differentiated from pluripotent stem cells, is likely to identify a large number of epigenetic drug targets. In contrast, targeted epigenomic editing of select genomic loci emerges in the animal model as a powerful tool to interfere with cognition and complex behaviors.
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ISSN:0890-8567
1527-5418