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dc.contributor.authorMitchell, Amanda C.
dc.contributor.authorBharadwaj, Rahul
dc.contributor.authorWhittle, Catheryne
dc.contributor.authorKrueger, Winfried
dc.contributor.authorMirnics, Karoly
dc.contributor.authorHurd, Yasmin
dc.contributor.authorRasmussen, Theodore
dc.contributor.authorAkbarian, Schahram
dc.date2022-08-11T08:08:56.000
dc.date.accessioned2022-08-23T16:12:32Z
dc.date.available2022-08-23T16:12:32Z
dc.date.issued2014-06-15
dc.date.submitted2015-09-21
dc.identifier.citationBiol Psychiatry. 2014 Jun 15;75(12):961-9. doi: 10.1016/j.biopsych.2013.07.015. Epub 2013 Aug 16. <a href="http://dx.doi.org/10.1016/j.biopsych.2013.07.015">Link to article on publisher's site</a>
dc.identifier.issn0006-3223 (Linking)
dc.identifier.doi10.1016/j.biopsych.2013.07.015
dc.identifier.pmid23958183
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33415
dc.description.abstractLess than 1.5% of the human genome encodes protein. However, vast portions of the human genome are subject to transcriptional and epigenetic regulation, and many noncoding regulatory DNA elements are thought to regulate the spatial organization of interphase chromosomes. For example, chromosomal "loopings" are pivotal for the orderly process of gene expression, by enabling distal regulatory enhancer or silencer elements to directly interact with proximal promoter and transcription start sites, potentially bypassing hundreds of kilobases of interspersed sequence on the linear genome. To date, however, epigenetic studies in the human brain are mostly limited to the exploration of DNA methylation and posttranslational modifications of the nucleosome core histones. In contrast, very little is known about the regulation of supranucleosomal structures. Here, we show that chromosome conformation capture, a widely used approach to study higher-order chromatin, is applicable to tissue collected postmortem, thereby informing about genome organization in the human brain. We introduce chromosome conformation capture protocols for brain and compare higher-order chromatin structures at the chromosome 6p22.2-22.1 schizophrenia and bipolar disorder susceptibility locus, and additional neurodevelopmental risk genes, (DPP10, MCPH1) in adult prefrontal cortex and various cell culture systems, including neurons derived from reprogrammed skin cells. We predict that the exploration of three-dimensional genome architectures and function will open up new frontiers in human brain research and psychiatric genetics and provide novel insights into the epigenetic risk architectures of regulatory noncoding DNA. All rights reserved.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23958183&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925763/
dc.subjectBioinformatics
dc.subjectGenetics and Genomics
dc.subjectGenomics
dc.subjectNeuroscience and Neurobiology
dc.subjectPsychiatry
dc.subjectPsychiatry and Psychology
dc.titleThe genome in three dimensions: a new frontier in human brain research
dc.typeJournal Article
dc.source.journaltitleBiological psychiatry
dc.source.volume75
dc.source.issue12
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1944
dc.identifier.contextkey7622796
html.description.abstract<p>Less than 1.5% of the human genome encodes protein. However, vast portions of the human genome are subject to transcriptional and epigenetic regulation, and many noncoding regulatory DNA elements are thought to regulate the spatial organization of interphase chromosomes. For example, chromosomal "loopings" are pivotal for the orderly process of gene expression, by enabling distal regulatory enhancer or silencer elements to directly interact with proximal promoter and transcription start sites, potentially bypassing hundreds of kilobases of interspersed sequence on the linear genome. To date, however, epigenetic studies in the human brain are mostly limited to the exploration of DNA methylation and posttranslational modifications of the nucleosome core histones. In contrast, very little is known about the regulation of supranucleosomal structures. Here, we show that chromosome conformation capture, a widely used approach to study higher-order chromatin, is applicable to tissue collected postmortem, thereby informing about genome organization in the human brain. We introduce chromosome conformation capture protocols for brain and compare higher-order chromatin structures at the chromosome 6p22.2-22.1 schizophrenia and bipolar disorder susceptibility locus, and additional neurodevelopmental risk genes, (DPP10, MCPH1) in adult prefrontal cortex and various cell culture systems, including neurons derived from reprogrammed skin cells. We predict that the exploration of three-dimensional genome architectures and function will open up new frontiers in human brain research and psychiatric genetics and provide novel insights into the epigenetic risk architectures of regulatory noncoding DNA. All rights reserved.</p>
dc.identifier.submissionpathgsbs_sp/1944
dc.contributor.departmentDepartment of Psychiatry
dc.contributor.departmentBrudnick Neuropsychiatric Research Institute
dc.source.pages961-9
dc.contributor.studentRahul Bharadwaj


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