Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain

By Alisa Mo, Eran A. Mukamel, Fred P. Davis, C. Luo, G. L. Henry, S. Picard, M. Urich, Joseph R. Nery, Terrence J. Sejnowski, Ryan Lister and 3 more. Neuron, 2015

703 citations recorded by the source corpus.

SUMMARY 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/61892e239cd341d565c4ea0e36779f4c05fb826e

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Multi-omics single-cell data integration and regulatory inference with graph-linked embedding (2022, background): “Unlike chromatin accessibility, gene body DNA methylation generally shows a negative correlation with gene expression in neuronal cells 39 .”
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