Layer-specific chromatin accessibility landscapes reveal regulatory networks in adult mouse visual cortex
Abstract
Mammalian cortex is a laminar structure, with each layer composed of a characteristic set of cell types with different morphological, electrophysiological, and connectional properties. Here, we define chromatin accessibility landscapes of major, layer-specific excitatory classes of neurons, and compare them to each other and to inhibitory cortical neurons using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We identify a large number of layer-specific accessible sites, and significant association with genes that are expressed in specific cortical layers. Integration of these data with layer-specific transcriptomic profiles and transcription factor binding motifs enabled us to construct a regulatory network revealing potential key layer-specific regulators, including Cux1/2, Foxp2, Nfia, Pou3f2, and Rorb. This dataset is a valuable resource for identifying candidate layer-specific cis-regulatory elements in adult mouse cortex.
Data availability
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Layer-specific ATAC-seq of the neurons of adult mouse visual cortex defined by Cre-driver linesPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE87548).
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Epigenomic Signatures of Neuronal Diversity in the Mammalian BrainPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE63137).
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Adult mouse cortical cell taxonomy by single cell transcriptomicsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE71585).
Article and author information
Author details
Funding
National Institute on Drug Abuse (1R01DA036909-01)
- Lucas T Gray
- Hongkui Zeng
- Bosiljka Tasic
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sean R Eddy, Howard Hughes Medical Institute, Harvard University, United States
Ethics
Animal experimentation: All mice were housed at the Allen Institute for Brain Science under Institutional Care and Use Committee protocols 0703, 1208, and 1508. No more than 5 animals per cage were maintained on a regular 12-h day/night cycle, with water and food provided ad libitum. All animal sacrifices were performed after careful isofluorane treatment to minimize suffering.
Version history
- Received: September 27, 2016
- Accepted: January 22, 2017
- Accepted Manuscript published: January 23, 2017 (version 1)
- Version of Record published: February 24, 2017 (version 2)
Copyright
© 2017, Gray et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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