Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-35384-1
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Funding
- NIH-NIDA Avenir Director's Pioneer Award [DP1 DA044250]
- NIDA Research Project Grant [1R01DA052465-01A1]
- Pilot Award from the Epigenetics Institute at the University of Pennsylvania, NIH Drug Abuse Dissertation Research Award [R36 DA050877]
- Children's Hospital of Philadelphia Postdoctoral Fellowship for Academic Diversity
- T32 Predoctoral Training Grant in Addiction [NIDA T32DA028874]
- SynGAP Research Fund Postdoctoral Fellowship
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The authors optimized a hybrid protocol, ICuRuS, to profile epigenetic features in neuronal subtypes from a single mouse. This method allows for robust epigenetic profiling at cell-type specific resolution.
Bulk or pooled epigenomic profiling in the heterogenous brain obscures cell-type-specificity and individual subject variability in gene regulation. Here the authors optimized a hybrid protocol, ICuRuS, to profile epigenetic features in neuronal subtypes from a single mouse. Epigenetic gene regulation in the heterogeneous brain remains challenging to decipher with current strategies. Bulk tissue analysis from pooled subjects reflects the average of cell-type specific changes across cell-types and individuals, which obscures causal relationships between epigenetic modifications, regulation of gene expression, and complex pathology. To address these limitations, we optimized a hybrid protocol, ICuRuS, for the isolation of nuclei tagged in specific cell-types and histone post translational modification profiling from the striatum of a single mouse. We combined affinity-based isolation of the medium spiny neuron subtypes, Adenosine 2a Receptor or Dopamine Receptor D1, with cleavage of histone-DNA complexes using an antibody-targeted micrococcal nuclease to release DNA complexes for paired end sequencing. Unlike fluorescence activated cell sorting paired with chromatin immunoprecipitation, ICuRuS allowed for robust epigenetic profiling at cell-type specific resolution. Our analysis provides a framework to understand combinatorial relationships between neuronal-subtype-specific epigenetic modifications and gene expression.
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