The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function
Open accessAbstract
Mutations of MECP2 ( Methyl-CpG Binding Protein 2 ) cause Rett syndrome. As a chromatin-associated multifunctional protein, how MeCP2 integrates external signals and regulates neuronal function remain unclear. Although neuronal activity-induced phosphorylation of MeCP2 at serine 421 (S421) has been reported, the full spectrum of MeCP2 phosphorylation together with the in vivo function of such modifications are yet to be revealed. Here, we report the identification of several MeCP2 phosphorylation sites in normal and epileptic brains from multiple species. We demonstrate that serine 80 (S80) phosphorylation of MeCP2 is critical as its mutation into alanine (S80A) in transgenic knock-in mice leads to locomotor deficits. S80A mutation attenuates MeCP2 chromatin association at several gene promoters in resting neurons and leads to transcription changes of a small number of genes. Calcium influx in neurons causes dephosphorylation at S80, potentially contributing to its dissociation from the chromatin. We postulate that phosphorylation of MeCP2 modulates its dynamic function in neurons transiting between resting and active states within neural circuits that underlie behaviors.
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Cites
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2
Amir, R. E., Van den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., & Zoghbi, H. Y. (1999) · Nature Genetics · doi:10.1038/13810 · Cited by 4,990
MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription
Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T. C., Qin, J., & Zoghbi, H. Y. (2008) · Science · doi:10.1126/science.1153252 · Cited by 1,823
DNA Methylation-Related Chromatin Remodeling in Activity-Dependent Bdnf Gene Regulation
Martinowich, K., Hattori, D., Wu, H., Fouse, S., He, F., Hu, Y., Fan, G., & Sun, Y. E. (2003) · Science · doi:10.1126/science.1090842 · Cited by 1,405
Self-citationDeficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice
Chen, R. Z., Akbarian, S., Tudor, M., & Jaenisch, R. (2001) · Nature Genetics · doi:10.1038/85906 · Cited by 1,275
Self-citationReversal of Neurological Defects in a Mouse Model of Rett Syndrome
Guy, J., Gan, J., Selfridge, J., Cobb, S., & Bird, A. (2007) · Science · doi:10.1126/science.1138389 · Cited by 1,230
CBP Histone Acetyltransferase Activity Is a Critical Component of Memory Consolidation
Korzus, E., Rosenfeld, M. G., & Mayford, M. (2004) · Neuron · doi:10.1016/j.neuron.2004.06.002 · Cited by 823
Dani, V. S., Chang, Q., Maffei, A., Turrigiano, G. G., Jaenisch, R., & Nelson, S. B. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506071102 · Cited by 639
Self-citationYoung, J. I., Hong, E. P., Castle, J. C., Crespo-Barreto, J., Bowman, A. B., Rose, M. F., Kang, D., Richman, R., Johnson, J. M., Berget, S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507856102 · Cited by 484
Kishi, N., & Macklis, J. D. (2004) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2004.07.006 · Cited by 445
Phosphorylation of CBP mediates transcriptional activation by neural activity and CaM kinase IV
Impey, S., Fong, A. L., Wang, Y., Cardinaux, J.-R., Fass, D. M., Obrietan, K., Wayman, G. A., Storm, D. R., Soderling, T. R., & Goodman, R. H. (2002) · Neuron · doi:10.1016/s0896-6273(02)00654-2 · Cited by 335
Cited by
DNA methylation and its basic function
Moore, L. D., Le, T., & Fan, G. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.112 · Cited by 4,906
Marchetto, M. C. N., Carromeu, C., Acab, A., Yu, D., Yeo, G. W., Mu, Y., Chen, G., Gage, F. H., & Muotri, A. R. (2010) · Cell · doi:10.1016/j.cell.2010.10.016 · Cited by 1,329
Zoghbi, H. Y., & Bear, M. F. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009886 · Cited by 797
Neuronal MeCP2 Is Expressed at Near Histone-Octamer Levels and Globally Alters the Chromatin State
Skene, P. J., Illingworth, R. S., Webb, S., Kerr, A. R. W., James, K. D., Turner, D. J., Andrews, R., & Bird, A. P. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.01.030 · Cited by 688
Epigenetic mechanisms in cognition
Day, J. J., & Sweatt, J. D. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.019 · Cited by 510
Metadata
- Authors
- Tao, J., Hu, K., Chang, Q., Wu, H., Sherman, N. E., Martinowich, K., Klose, R. J., Schanen, C., Jaenisch, R., Wang, W., & Sun, Y. E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-03-24
- Volume
- 106
- Issue
- 12
- Pages
- 4882-4887
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2170015414
- Cited by
- 226
- References
- 13
- FWCI
- 11.58
- Type
- journal article
- Language
- en
- Open access
- green
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- Tao, J., Hu, K., Chang, Q., Wu, H., Sherman, N. E., Martinowich, K., Klose, R. J., Schanen, C., Jaenisch, R., Wang, W., & Sun, Y. E. (2009). Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0811648106
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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