Layer-specific chromatin accessibility landscapes reveal regulatory networks in adult mouse visual cortex
- Allen Institute for Brain Science, United States
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
-
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).
-
Epigenomic Signatures of Neuronal Diversity in the Mammalian BrainPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE63137).
-
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.
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.
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.
Metrics
-
- 7,844
- views
-
- 1,424
- downloads
-
- 72
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Layer-specific chromatin accessibility landscapes reveal regulatory networks in adult mouse visual cortex
eLife 6:e21883.
https://doi.org/10.7554/eLife.21883
Further reading
-
- Computational and Systems Biology
- Genetics and Genomics
Root causal gene expression levels – or root causal genes for short – correspond to the initial changes to gene expression that generate patient symptoms as a downstream effect. Identifying root causal genes is critical towards developing treatments that modify disease near its onset, but no existing algorithms attempt to identify root causal genes from data. RNA-sequencing (RNA-seq) data introduces challenges such as measurement error, high dimensionality and non-linearity that compromise accurate estimation of root causal effects even with state-of-the-art approaches. We therefore instead leverage Perturb-seq, or high-throughput perturbations with single-cell RNA-seq readout, to learn the causal order between the genes. We then transfer the causal order to bulk RNA-seq and identify root causal genes specific to a given patient for the first time using a novel statistic. Experiments demonstrate large improvements in performance. Applications to macular degeneration and multiple sclerosis also reveal root causal genes that lie on known pathogenic pathways, delineate patient subgroups and implicate a newly defined omnigenic root causal model.
-
- Chromosomes and Gene Expression
- Genetics and Genomics
A new method for mapping torsion provides insights into the ways that the genome responds to the torsion generated by RNA polymerase II.
