Satb2 determines miRNA expression and long-term memory in the adult central nervous system
- Medical University of Innsbruck, Austria
- University of Innsbruck, Austria
- Technical University Braunschweig, Germany
- German Center for Neurodegenerative Diseases, Germany
Abstract
SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.
Data availability
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The Schizophrenia Risk Gene Product Satb2 Regulates miRNAs Expression and Long-Term Memory in Adult CNSPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE77005).
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A Novel Neuron-specific Histone H4K20 Demethylase LSD1n Promotes Transcriptional Elongation and is Essential for Learning and MemoryPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE63271).
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LRP8-Reelin-regulated Neuronal (LRN) Enhancer signature underlying learning and memory formation (ChIP-Seq)Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE66701).
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Widespread transcription at neuronal activity-regulated enhancersPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE21161).
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Conserved epigenomic signatures between mouse and human elucidate immune basis of Alzheimer's diseasePublicly available at the NCBI Gene Expression Omnibus (accession no: GSE65159).
Article and author information
Author details
Funding
Austrian Science Fund (P25014-B24)
- Galina Apostolova
Austrian Science Fund (DK W1206)
- Georg Dechant
Austrian Science Fund (DK W1206)
- Nicolas Singewald
Deutsche Forschungsgemeinschaft
- Martin Korte
Innsbruck Medical University (MUI-Start 2010012004)
- Galina Apostolova
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Anne West, Duke University School of Medicine, United States
Ethics
Animal experimentation: All animal experimentation procedures were approved by the Austrian Animal Experimentation Ethics Board (Permit Number: GZ: BMWFW-66.011/0078-WF/II/3b/2014)
Version history
- Received: April 28, 2016
- Accepted: November 28, 2016
- Accepted Manuscript published: November 29, 2016 (version 1)
- Version of Record published: January 3, 2017 (version 2)
Copyright
© 2016, Jaitner et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Satb2 determines miRNA expression and long-term memory in the adult central nervous system
eLife 5:e17361.
https://doi.org/10.7554/eLife.17361
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