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Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA

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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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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.

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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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