Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain

Alisa Mo, Eran A. Mukamel, Fred P. Davis, Chongyuan Luo, Gilbert L. Henry, Serge Picard, Mark A. Urich, Joseph R. Nery, Terrence J. Sejnowski, Ryan Lister, Sean R. Eddy, Joseph R. Ecker, Jeremy Nathans

Research output: Contribution to journalArticle

Abstract

Neuronal diversity is essential for mammalian brain function but poses a challenge to molecular profiling. To address the need for tools that facilitate cell-type-specific epigenomic studies, we developed the first affinity purification approach to isolate nuclei from genetically defined cell types in a mammal. We combine this technique with next-generation sequencing to show that three subtypes of neocortical neurons have highly distinctive epigenomic landscapes. Over 200,000 regions differ in chromatin accessibility and DNA methylation signatures characteristic of gene regulatory regions. By footprinting and motif analyses, these regions are predicted to bind distinct cohorts of neuron subtype-specific transcription factors. Neuronal epigenomes reflect both past and present gene expression, with DNA hyper-methylation at developmentally critical genes appearing as a novel epigenomic signature in mature neurons. Taken together, our findings link the functional and transcriptional complexity of neurons to their underlying epigenomic diversity. Mo et al. develop a broadly applicable tool to purify genetically labeled nuclei in mice and, using genome-wide maps of gene expression, DNA methylation, and chromatin accessibility, show how three neuronal subtypes adopt distinct epigenomic configurations associated with function and development.

Original languageEnglish (US)
Pages (from-to)1369-1384
Number of pages16
JournalNeuron
Volume86
Issue number6
DOIs
StatePublished - Jun 17 2015

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Epigenomics
DNA Methylation
Brain
Neurons
Chromatin
Gene Expression
Nucleic Acid Regulatory Sequences
Genes
Mammals
Transcription Factors
Genome

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mo, A., Mukamel, E. A., Davis, F. P., Luo, C., Henry, G. L., Picard, S., ... Nathans, J. (2015). Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain. Neuron, 86(6), 1369-1384. https://doi.org/10.1016/j.neuron.2015.05.018

Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain. / Mo, Alisa; Mukamel, Eran A.; Davis, Fred P.; Luo, Chongyuan; Henry, Gilbert L.; Picard, Serge; Urich, Mark A.; Nery, Joseph R.; Sejnowski, Terrence J.; Lister, Ryan; Eddy, Sean R.; Ecker, Joseph R.; Nathans, Jeremy.

In: Neuron, Vol. 86, No. 6, 17.06.2015, p. 1369-1384.

Research output: Contribution to journalArticle

Mo, A, Mukamel, EA, Davis, FP, Luo, C, Henry, GL, Picard, S, Urich, MA, Nery, JR, Sejnowski, TJ, Lister, R, Eddy, SR, Ecker, JR & Nathans, J 2015, 'Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain', Neuron, vol. 86, no. 6, pp. 1369-1384. https://doi.org/10.1016/j.neuron.2015.05.018
Mo A, Mukamel EA, Davis FP, Luo C, Henry GL, Picard S et al. Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain. Neuron. 2015 Jun 17;86(6):1369-1384. https://doi.org/10.1016/j.neuron.2015.05.018
Mo, Alisa ; Mukamel, Eran A. ; Davis, Fred P. ; Luo, Chongyuan ; Henry, Gilbert L. ; Picard, Serge ; Urich, Mark A. ; Nery, Joseph R. ; Sejnowski, Terrence J. ; Lister, Ryan ; Eddy, Sean R. ; Ecker, Joseph R. ; Nathans, Jeremy. / Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain. In: Neuron. 2015 ; Vol. 86, No. 6. pp. 1369-1384.
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