Epigenetics in the human brain
Department of Psychiatry, Brudnick Neuropsychiatric Research Institute; Program in Molecular Medicine
Medical Subject Headings
Brain Chemistry; DNA Methylation; Epigenesis, Genetic; Humans; Mental Disorders
Cell and Developmental Biology | Mental Disorders | Molecular and Cellular Neuroscience | Neuroscience and Neurobiology | Psychiatry | Psychiatry and Psychology
Many cellular constituents in the human brain permanently exit from the cell cycle during pre- or early postnatal development, but little is known about epigenetic regulation of neuronal and glial epigenomes during maturation and aging, including changes in mood and psychosis spectrum disorders and other cognitive or emotional disease. Here, we summarize the current knowledge base as it pertains to genome organization in the human brain, including the regulation of DNA cytosine methylation and hydroxymethylation, and a subset of (altogether >100) residue-specific histone modifications associated with gene expression, and silencing and various other functional chromatin states. We propose that high-resolution mapping of epigenetic markings in postmortem brain tissue or neural cultures derived from induced pluripotent cells (iPS), in conjunction with transcriptome profiling and whole-genome sequencing, will increasingly be used to define the molecular pathology of specific cases diagnosed with depression, schizophrenia, autism, or other major psychiatric disease. We predict that these highly integrative explorations of genome organization and function will provide an important alternative to conventional approaches in human brain studies, which mainly are aimed at uncovering group effects by diagnosis but generally face limitations because of cohort size.
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Citation: Neuropsychopharmacology. 2013 Jan;38(1):183-97. doi: 10.1038/npp.2012.78. Link to article on publisher's site
Houston, Isaac B.; Peter, Cyril J.; Mitchell, Amanda C.; Straubhaar, Juerg R.; Rogaev, Evgeny I.; and Akbarian, Schahram, "Epigenetics in the human brain" (2013). University of Massachusetts Medical School Faculty Publications. 243.