Longitudinal assessment of neuronal 3D genomes in mouse prefrontal cortex

Amanda C. Mitchell, Behnam Javidfar, Lucy K. Bicks, Rachael Neve, Krassimira Garbett, Sharon S. Lander, K. Mirnics, Hirofumi Morishita, Marcelo A. Wood, Yan Jiang, Inna Gaisler-Salomon, Schahram Akbarian

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 Gmethyl 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.

Original languageEnglish
Article number12743
JournalNature Communications
Volume7
DOIs
Publication statusPublished - Sep 6 2016

Fingerprint

genome
cortexes
Prefrontal Cortex
genes
brain
mice
Genes
Genome
cognition
Bacterial DNA
chromatin
dams
Conformations
chromosomes
Brain
adenines
Brain Diseases
Proxy
Adenine
N-Methyl-D-Aspartate Receptors

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Mitchell, A. C., Javidfar, B., Bicks, L. K., Neve, R., Garbett, K., Lander, S. S., ... Akbarian, S. (2016). Longitudinal assessment of neuronal 3D genomes in mouse prefrontal cortex. Nature Communications, 7, [12743]. https://doi.org/10.1038/ncomms12743

Longitudinal assessment of neuronal 3D genomes in mouse prefrontal cortex. / Mitchell, Amanda C.; Javidfar, Behnam; Bicks, Lucy K.; Neve, Rachael; Garbett, Krassimira; Lander, Sharon S.; Mirnics, K.; Morishita, Hirofumi; Wood, Marcelo A.; Jiang, Yan; Gaisler-Salomon, Inna; Akbarian, Schahram.

In: Nature Communications, Vol. 7, 12743, 06.09.2016.

Research output: Contribution to journalArticle

Mitchell, AC, Javidfar, B, Bicks, LK, Neve, R, Garbett, K, Lander, SS, Mirnics, K, Morishita, H, Wood, MA, Jiang, Y, Gaisler-Salomon, I & Akbarian, S 2016, 'Longitudinal assessment of neuronal 3D genomes in mouse prefrontal cortex', Nature Communications, vol. 7, 12743. https://doi.org/10.1038/ncomms12743
Mitchell AC, Javidfar B, Bicks LK, Neve R, Garbett K, Lander SS et al. Longitudinal assessment of neuronal 3D genomes in mouse prefrontal cortex. Nature Communications. 2016 Sep 6;7. 12743. https://doi.org/10.1038/ncomms12743
Mitchell, Amanda C. ; Javidfar, Behnam ; Bicks, Lucy K. ; Neve, Rachael ; Garbett, Krassimira ; Lander, Sharon S. ; Mirnics, K. ; Morishita, Hirofumi ; Wood, Marcelo A. ; Jiang, Yan ; Gaisler-Salomon, Inna ; Akbarian, Schahram. / Longitudinal assessment of neuronal 3D genomes in mouse prefrontal cortex. In: Nature Communications. 2016 ; Vol. 7.
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