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| Status |
Public on Dec 31, 2017 |
| Title |
Neuronal activity, TGFβ signaling and unpredictable chronic stress affect transcription of Gadd45 family members in vitro and in vivo [MeDIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
Neuronal activity is altered in several neurological and psychiatric diseases. Upon depolarization not only neurotransmitters are released but also cytokines and other activators of signaling cascades. Unraveling their complex implication in transcriptional control in receiving cells will contribute to understand specific central nervous system (CNS) pathologies and will be of therapeutical interest. In this study we depolarized mature hippocampal neurons in vitro using KCl and revealed increased release not only of Brain-derived neurotrophic factor (BDNF), but also of Transforming growth factor beta (TGFB). Neuronal activity together with BDNF and TGFB controls transcription of DNA modifying enzymes specifically members of the DNA-damage-inducible (Gadd) family, Gadd45a, Gadd45b, and Gadd45g. MeDIP followed by massive parallel sequencing and transcriptome analyses revealed less DNA methylation upon KCl treatment. Thereby, psychiatric disorder-related genes, namely Tshz1, Foxn3, Jarid2, Per1, Map3k5, and Arc are transcriptionally activated and demethylated upon neuronal activation. To analyze whether misexpression of Gadd45 family members can be associated with psychiatric diseases, we applied unpredictable chronic mild stress (UCMS) as established model for depression to mice.UCMS lead to a reduced expression of Gadd45 family members. Taken together, our data demonstrate that Gadd45 family members are new putative targets for UCMS treatments.
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| Overall design |
Definition of activity dependent targets on transcriptional and DNA methylation level
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| Contributor(s) |
Franz H, Bovio P, Grassi D, Vogel T, Vezzali R |
| Citation missing |
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| Submission date |
Nov 25, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Henriette Franz |
| Organization name |
University Freiburg
|
| Department |
Anatomy and Cellbiology
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| Lab |
Vogel
|
| Street address |
Alberstr: 17
|
| City |
Freiburg |
| ZIP/Postal code |
79104 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (7)
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| This SubSeries is part of SuperSeries: |
| GSE90513 |
Neuronal activity, TGFβ signaling and unpredictable chronic stress affect transcription of Gadd45 family members in vitro and in vivo |
|
| Relations |
| BioProject |
PRJNA354944 |
| SRA |
SRP093914 |
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