Intronic enhancer region governs transcript-specific Bdnf expression in rodent neurons
- Tallinn University of Technology, Estonia
- Kings College London, United Kingdom
Abstract
Brain-derived neurotrophic factor (BDNF) controls the survival, growth, and function of neurons both during the development and in the adult nervous system. Bdnf is transcribed from several distinct promoters generating transcripts with alternative 5' exons. Bdnf transcripts initiated at the first cluster of exons have been associated with the regulation of body weight and various aspects of social behavior, but the mechanisms driving the expression of these transcripts have remained poorly understood. Here, we identify an evolutionarily conserved intronic enhancer region inside the Bdnf gene that regulates both basal and stimulus-dependent expression of the Bdnf transcripts starting from the first cluster of 5' exons in mouse and rat neurons. We further uncover a functional E-box element in the enhancer region, linking the expression of Bdnf and various pro-neural basic helix-loop-helix transcription factors. Collectively, our results shed new light on the cell-type- and stimulus-specific regulation of the important neurotrophic factor BDNF.
Data availability
Mass-spectrometry results of the in vitro DNA pulldown experiment are provided in Supplementary Table 3.
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Widespread transcription at neuronal activity-regulated enhancersNCBI Gene Expression Omnibus, GSE21161.
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Rapid and Pervasive Changes in Genome-Wide Enhancer Usage During Mammalian DevelopmentNCBI Gene Expression Omnibus, GSE52386.
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Genome-wide identification and characterization of functional neuronal activity-dependent enhancersNCBI Gene Expression Omnibus, GSE60192.
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NeuroD2 ChIP-SEQ from embryonic cortexNCBI Gene Expression Omnibus, GSE67539.
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A protein interaction network of mental disorder factors in neural stem cellsNCBI Gene Expression Omnibus, GSE70872.
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Genome-wide maps of EGR1 binding in mouse frontal cortexNCBI Gene Expression Omnibus, GSE67482.
Article and author information
Author details
Funding
Estonian Research Council (IUT19-18)
- Jürgen Tuvikene
- Eli-Eelika Esvald
- Annika Rähni
- Kaie Uustalu
- Annela Avarlaid
- Tõnis Timmusk
Estonian Research Council (PRG805)
- Jürgen Tuvikene
- Eli-Eelika Esvald
- Annela Avarlaid
- Tõnis Timmusk
Norwegian Financial Mechanism (EMP128)
- Jürgen Tuvikene
- Eli-Eelika Esvald
- Annika Rähni
- Kaie Uustalu
- Tõnis Timmusk
European Regional Development Fund (2014-2020.4.01.15-0012)
- Jürgen Tuvikene
- Eli-Eelika Esvald
- Annika Rähni
- Kaie Uustalu
- Annela Avarlaid
- Tõnis Timmusk
H2020-MSCA-RISE-2016 (EU734791)
- Jürgen Tuvikene
- Eli-Eelika Esvald
- Anna Zhuravskaya
- Annela Avarlaid
- Eugene V Makeyev
- Tõnis Timmusk
Biotechnology and Biological Sciences Research Council (BB/M001199/1)
- Anna Zhuravskaya
- Eugene V Makeyev
Biotechnology and Biological Sciences Research Council (BB/M007103/1)
- Anna Zhuravskaya
- Eugene V Makeyev
Biotechnology and Biological Sciences Research Council (BB/R001049/1)
- Anna Zhuravskaya
- Eugene V Makeyev
European Regional Development Fund (ASTRA 2014-2020.4.01.16-0032)
- Jürgen Tuvikene
- Eli-Eelika Esvald
- Annela Avarlaid
- Tõnis Timmusk
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Anne E West, Duke University School of Medicine, United States
Publication history
- Received: November 25, 2020
- Accepted: February 8, 2021
- Accepted Manuscript published: February 9, 2021 (version 1)
- Version of Record published: February 18, 2021 (version 2)
Copyright
© 2021, Tuvikene 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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Intronic enhancer region governs transcript-specific Bdnf expression in rodent neurons
eLife 10:e65161.
https://doi.org/10.7554/eLife.65161
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