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Open AccessArticle

Mechanistic Insights in NeuroD Potentiation of Mineralocorticoid Receptor Signaling

1
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
2
Department of Cognitive Neuroscience, Radboudumc, 6525 GA Nijmegen, The Netherlands
3
Donders Institute for Brain, Cognition and Behaviour, Radboud University, 6525 EN Nijmegen, The Netherlands
4
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(7), 1575; https://doi.org/10.3390/ijms20071575
Received: 1 March 2019 / Revised: 24 March 2019 / Accepted: 25 March 2019 / Published: 29 March 2019
(This article belongs to the Special Issue Molecular Psychiatry)
Mineralocorticoid receptor (MR)-mediated signaling in the brain has been suggested as a protective factor in the development of psychopathology, in particular mood disorders. We recently identified genomic loci at which either MR or the closely related glucocorticoid receptor (GR) binds selectively, and found members of the NeuroD transcription factor family to be specifically associated with MR-bound DNA in the rat hippocampus. We show here using forebrain-specific MR knockout mice that GR binding to MR/GR joint target loci is not affected in any major way in the absence of MR. Neurod2 binding was also independent of MR binding. Moreover, functional comparison with MyoD family members indicates that it is the chromatin remodeling aspect of NeuroD, rather than its direct stimulation of transcription, that is responsible for potentiation of MR-mediated transcription. These findings suggest that NeuroD acts in a permissive way to enhance MR-mediated transcription, and they argue against competition for DNA binding as a mechanism of MR- over GR-specific binding. View Full-Text
Keywords: basic-helix-loop-helix; brain; coactivator; glucocorticoids; hippocampus; mineralocorticoid receptor knockout; stress; transcription biology basic-helix-loop-helix; brain; coactivator; glucocorticoids; hippocampus; mineralocorticoid receptor knockout; stress; transcription biology
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van Weert, L.T.C.M.; Buurstede, J.C.; Sips, H.C.M.; Mol, I.M.; Puri, T.; Damsteegt, R.; Roozendaal, B.; Sarabdjitsingh, R.A.; Meijer, O.C. Mechanistic Insights in NeuroD Potentiation of Mineralocorticoid Receptor Signaling. Int. J. Mol. Sci. 2019, 20, 1575.

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