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Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA

Abstract

Both increases and decreases in methyl CpG–binding protein 2 (MeCP2) levels cause neurodevelopmental defects. We found that MeCP2 translation is regulated by microRNA 132 (miR132). Block of miR132-mediated repression increased MeCP2 and brain-derived neurotrophic factor (BDNF) levels in cultured rat neurons and the loss of MeCP2 reduced BDNF and miR132 levels in vivo. This feedback loop may provide a mechanism for homeostatic control of MeCP2 expression.

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Figure 1: miR132 controls MeCP2 protein levels in postnatal day 1 cortical neurons.
Figure 2: MeCP2 induces expression of target genes.

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Acknowledgements

We thank Q. Zhang for the experiments examining CtBP. This work was supported by grants from the US National Institutes of Health and the Rett Syndrome Research Foundation.

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Authors

Contributions

M.E.K., D.T.L. and R.H.G. designed the experiments. M.E.K., D.T.L. and L.M. carried out the experiments. M.E.K., D.T.L., L.M., S.I., G.M. and R.H.G. wrote the paper.

Corresponding author

Correspondence to Richard H Goodman.

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Klein, M., Lioy, D., Ma, L. et al. Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA. Nat Neurosci 10, 1513–1514 (2007). https://doi.org/10.1038/nn2010

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