RT Journal Article
SR Electronic
T1 Cell-Type Specific Profiling of Histone Post-Translational Modifications in the Adult Mouse Striatum
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.17.476614
DO 10.1101/2022.01.17.476614
A1 Marco D. Carpenter
A1 Delaney K. Fischer
A1 Shuo Zhang
A1 Allison M Bond
A1 Kyle S. Czarnecki
A1 Morgan T. Woolf
A1 Hongjun Song
A1 Elizabeth A. Heller
YR 2022
UL http://biorxiv.org/content/early/2022/01/20/2022.01.17.476614.abstract
AB Histone post-translational modifications (hPTMs) regulate gene expression via changes in chromatin accessibility and transcription factor recruitment. At a given locus, the coordinated enrichment of several distinct hPTMs regulate gene expression in response to external stimuli. However, neuronal hPTMs have been primarily characterized in bulk brain tissue and/or tissue pooled across subjects. This obscures both cell-type and individual variability, features essential to understand individual susceptibility to psychiatric disease. To address this limitation, we optimized a hybrid protocol, ICuRuS, to profile both activating and repressive hPTMs in neuronal subtypes from a single mouse. We report here profiling of striatal medium spiny neuron (MSN) subtypes, genetically defined by expression of Adenosine 2a Receptor (A2a) or Dopamine Receptor D1 (D1), which differentially regulate reward processing and pathophysiology. Using ICuRuS, we defined genome-wide, A2a- or D1-specific combinatorial hPTM profiles, and discovered regulatory epigenomic features at genes implicated in neurobiological function and disease.Competing Interest StatementThe authors have declared no competing interest.