A comprehensive map coupling histone modifications with gene regulation in adult dopaminergic and serotonergic neurons

Erik Södersten (), Konstantinos Toskas, Vilma Rraklli, Katarina Tiklova, Åsa K. Björklund, Markus Ringnér, Thomas Perlmann and Johan Holmberg ()
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Erik Södersten: Ludwig Institute for Cancer Research, Karolinska Institutet
Konstantinos Toskas: Ludwig Institute for Cancer Research, Karolinska Institutet
Vilma Rraklli: Ludwig Institute for Cancer Research, Karolinska Institutet
Katarina Tiklova: Ludwig Institute for Cancer Research, Karolinska Institutet
Åsa K. Björklund: Uppsala University
Markus Ringnér: Lund University
Thomas Perlmann: Ludwig Institute for Cancer Research, Karolinska Institutet
Johan Holmberg: Ludwig Institute for Cancer Research, Karolinska Institutet

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract The brain is composed of hundreds of different neuronal subtypes, which largely retain their identity throughout the lifespan of the organism. The mechanisms governing this stability are not fully understood, partly due to the diversity and limited size of clinically relevant neuronal populations, which constitute a technical challenge for analysis. Here, using a strategy that allows for ChIP-seq combined with RNA-seq in small neuronal populations in vivo, we present a comparative analysis of permissive and repressive histone modifications in adult midbrain dopaminergic neurons, raphe nuclei serotonergic neurons, and embryonic neural progenitors. Furthermore, we utilize the map generated by our analysis to show that the transcriptional response of midbrain dopaminergic neurons following 6-OHDA or methamphetamine injection is characterized by increased expression of genes with promoters dually marked by H3K4me3/H3K27me3. Our study provides an in vivo genome-wide analysis of permissive/repressive histone modifications coupled to gene expression in these rare neuronal subtypes.

Date: 2018
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DOI: 10.1038/s41467-018-03538-9

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