title: The future of neuroepigenetics in the human brain.
abstract: Complex mechanisms shape the genome of brain cells into transcriptional units, clusters of condensed chromatin, and many other features that distinguish between various cell types and developmental stages sharing the same genetic material. Only a few years ago, the field's focus was almost entirely on a single mark, CpG methylation; the emerging complexity of neuronal and glial epigenomes now includes multiple types of DNA cytosine methylation, more than 100 residue-specific posttranslational histone modifications and histone variants, all of which superimposed by a dynamic and highly regulated three-dimensional organization of the chromosomal material inside the cell nucleus. Here, we provide an update on the most innovative approaches in neuroepigenetics and their potential contributions to approach cognitive functions and disorders unique to human. We propose that comprehensive, cell type-specific mappings of DNA and histone modifications, chromatin-associated RNAs, and chromosomal "loopings" and other determinants of three-dimensional genome organization will critically advance insight into the pathophysiology of the disease. For example, superimposing the epigenetic landscapes of neuronal and glial genomes onto genetic maps for complex disorders, ranging from Alzheimer's disease to schizophrenia, could provide important clues about neurological function for some of the risk-associated noncoding sequences in the human genome.
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Mitchell
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Panos
authors.initials: P
authors.lastname: Roussos
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Cyril
authors.initials: C
authors.lastname: Peter
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Nadejda
authors.initials: N
authors.lastname: Tsankova
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Schahram
authors.initials: S
authors.lastname: Akbarian
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D044127:Epigenesis, Genetic; D056726:Genetic Association Studies; D006801:Humans
chemical_list: D015415:Biomarkers; D002843:Chromatin
keywords: Cell type-specific chromatin profiling; Chromosome conformation; Epigenome; Human brain; Neuropsychiatric disease; iPS