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

Södersten, Erik; Toskas, Konstantinos; Rraklli, Vilma; Tiklova, Katarina; Björklund, Åsa K.; Ringnér, Markus LU ; Perlmann, Thomas and Holmberg, Johan (2018) In Nature Communications 9(1).
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... (More)

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.

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author
organization
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Contribution to journal
publication status
published
subject
in
Nature Communications
volume
9
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85044514368
ISSN
2041-1723
DOI
10.1038/s41467-018-03538-9
language
English
LU publication?
yes
id
2224c26a-7c87-42f9-8996-3782a7af3472
date added to LUP
2018-04-10 09:45:43
date last changed
2018-07-11 03:00:14
@article{2224c26a-7c87-42f9-8996-3782a7af3472,
  abstract     = {<p>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.</p>},
  articleno    = {1226},
  author       = {Södersten, Erik and Toskas, Konstantinos and Rraklli, Vilma and Tiklova, Katarina and Björklund, Åsa K. and Ringnér, Markus and Perlmann, Thomas and Holmberg, Johan},
  issn         = {2041-1723},
  language     = {eng},
  month        = {03},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {A comprehensive map coupling histone modifications with gene regulation in adult dopaminergic and serotonergic neurons},
  url          = {http://dx.doi.org/10.1038/s41467-018-03538-9},
  volume       = {9},
  year         = {2018},
}