Longitudinal assessment of neuronal 3D genomes in mouse prefrontal cortex
| Autor: | Sharon S Lander, Rachael L. Neve, Lucy K. Bicks, Krassimira A. Garbett, Yan Jiang, Schahram Akbarian, Amanda C. Mitchell, Karoly Mirnics, Behnam Javidfar, Hirofumi Morishita, Marcelo A. Wood, Inna Gaisler-Salomon |
|---|---|
| Přispěvatelé: | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Neve, Rachael L. |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Site-Specific DNA-Methyltransferase (Adenine-Specific) Science General Physics and Astronomy Prefrontal Cortex Biology Genome Receptors N-Methyl-D-Aspartate General Biochemistry Genetics and Molecular Biology GAD1 Article Epigenesis Genetic Chromosome conformation capture 03 medical and health sciences Mice Cognition Memory Animals Epigenetics Longitudinal Studies Prefrontal cortex Gene Genetics Chromosome Aberrations Neurons Multidisciplinary Staining and Labeling Glutamate Decarboxylase General Chemistry Epigenome Chromatin 030104 developmental biology Gene Expression Regulation Dizocilpine Maleate Neuroscience |
| Zdroj: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-10 (2016) Mitchell, AC; Javidfar, B; Bicks, LK; Neve, R; Garbett, K; Lander, SS; et al.(2016). Longitudinal assessment of neuronal 3D genomes in mouse prefrontal cortex. NATURE COMMUNICATIONS, 7. doi: 10.1038/ncomms12743. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/0sw590pg Nature |
| ISSN: | 2041-1723 |
| Popis: | Neuronal epigenomes, including chromosomal loopings moving distal cis-regulatory elements into proximity of target genes, could serve as molecular proxy linking present-day-behaviour to past exposures. However, longitudinal assessment of chromatin state is challenging, because conventional chromosome conformation capture assays essentially provide single snapshots at a given time point, thus reflecting genome organization at the time of brain harvest and therefore are non-informative about the past. Here we introduce ‘NeuroDam’ to assess epigenome status retrospectively. Short-term expression of the bacterial DNA adenine methyltransferase Dam, tethered to the Gad1 gene promoter in mouse prefrontal cortex neurons, results in stable G[superscriptmethyl]ATC tags at Gad1-bound chromosomal contacts. We show by NeuroDam that mice with defective cognition 4 months after pharmacological NMDA receptor blockade already were affected by disrupted chromosomal conformations shortly after drug exposure. Retrospective profiling of neuronal epigenomes is likely to illuminate epigenetic determinants of normal and diseased brain development in longitudinal context. United States. National Institutes of Health |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|