Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2
Open accessAbstract
Rett syndrome (RTT) is a postnatal neurodevelopmental disorder characterized by the loss of acquired motor and language skills, autistic features, and unusual stereotyped movements. RTT is caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). Mutations in MECP2 cause a variety of neurodevelopmental disorders including X-linked mental retardation, psychiatric disorders, and some cases of autism. Although MeCP2 was identified as a methylation-dependent transcriptional repressor, transcriptional profiling of RNAs from mice lacking MeCP2 did not reveal significant gene expression changes, suggesting that MeCP2 does not simply function as a global repressor. Changes in expression of a few genes have been observed, but these alterations do not explain the full spectrum of Rett-like phenotypes, raising the possibility that additional MeCP2 functions play a role in pathogenesis. In this study, we show that MeCP2 interacts with the RNA-binding protein Y box-binding protein 1 and regulates splicing of reporter minigenes. Importantly, we found aberrant alternative splicing patterns in a mouse model of RTT. Thus, we uncovered a previously uncharacterized function of MeCP2 that involves regulation of splicing, in addition to its role as a transcriptional repressor.
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MeCP2 may also facilitate transcriptional activation, chromatin compaction and mRNA splicing, while interacting with other regulatory proteins.
“However, MeCP2 may also facilitate transcriptional activation [77], chromatin compaction [78,79] and mRNA splicing [80,81], while also interacting with a host of other regulatory proteins involved in a variety of molecular pathways [81–84].”
From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [81]
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Cites
DNA Methylation-Related Chromatin Remodeling in Activity-Dependent <i>Bdnf</i> 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 · see citing works
Buckanovich, R., Yang, Y., & Darnell, R. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-03-01114.1996 · Cited by 192 · see citing works
Khandjian, E. W., Huot, M.-E., Tremblay, S., Davidovic, L., Mazroui, R., & Bardoni, B. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405398101 · Cited by 178 · see citing works
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- [66]Khandjian, E. W., Huot, M.-E., Tremblay, S., Davidovic, L., Mazroui, R. & Bardoni, B. (2004) Proc. Natl. Acad. Sci. USA 101, 13357-13362.
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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 · see citing works
Sharova, L. V., Sharov, A. A., Nedorezov, T., Piao, Y., Shaik, N., & Ko, M. S. H. (2009) · DNA Research · doi:10.1093/dnares/dsn030 · Cited by 591 · see citing works
Maunakea, A. K., Chepelev, I., Cui, K., & Zhao, K. (2013) · Cell Research · doi:10.1038/cr.2013.110 · Cited by 552 · see citing works
Environment and Brain Plasticity: Towards an Endogenous Pharmacotherapy
Sale, A., Berardi, N., & Maffei, L. (2014) · Physiological Reviews · doi:10.1152/physrev.00036.2012 · Cited by 402 · see citing works
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Baroncelli, L., Braschi, C., Spolidoro, M., Begenisic, T., Sale, A., & Maffei, L. (2010) · Cell Death & Differentiation · doi:10.1038/cdd.2009.193 · Cited by 330 · see citing works
Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2
Liu, Z., Li, X., Zhang, J.-T., Cai, Y.-J., Cheng, T.-L., Cheng, C., Wang, Y., Zhang, C.-C., Nie, Y.-H., Chen, Z.-F., et al. (2016) · Nature · doi:10.1038/nature16533 · Cited by 322 · see citing works
Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2
Giacometti, E., Luikenhuis, S., Beard, C., & Jaenisch, R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610593104 · Cited by 271 · see citing works
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Grafodatskaya, D., Chung, B., Szatmari, P., & Weksberg, R. (2010) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2010.05.005 · Cited by 235 · see citing works
An epigenetic framework for neurodevelopmental disorders: From pathogenesis to potential therapy
Millan, M. J. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.11.015 · Cited by 229 · see citing works
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Kyle, S. M., Vashi, N., & Justice, M. J. (2018) · Open Biology · doi:10.1098/rsob.170216 · Cited by 213 · see citing works
DNA methylation in social insects: how epigenetics can control behavior and longevity
Yan, H., Bonasio, R., Simola, D. F., Liebig, J., Berger, S. L., & Reinberg, D. (2015) · Annual Review of Entomology · doi:10.1146/annurev-ento-010814-020803 · Cited by 183 · see citing works
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Qureshi, I. A., & Mehler, M. F. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.02.005 · Cited by 112 · see citing works
Evolving Role of MeCP2 in Rett syndrome and Autism
LaSalle, J. M., & Yasui, D. H. (2009) · Epigenomics · doi:10.2217/epi.09.13 · Cited by 98 · see citing works
MeCP2 modulates gene expression pathways in astrocytes
Yasui, D. H., Xu, H., Dunaway, K. W., LaSalle, J. M., Jin, L.-W., & Maezawa, I. (2013) · Molecular Autism · doi:10.1186/2040-2392-4-3 · Cited by 90 · see citing works
Pacheco, N. L., Heaven, M. R., Holt, L. M., Crossman, D. K., Boggio, K. J., Shaffer, S. A., Flint, D. L., & Olsen, M. L. (2017) · Molecular Autism · doi:10.1186/s13229-017-0174-4 · Cited by 90 · see citing works
MECP2 Isoform-Specific Vectors with Regulated Expression for Rett Syndrome Gene Therapy
Rastegar, M., Hotta, A., Pasceri, P., Makarem, M., Cheung, A. Y. L., Elliott, S., Park, K. J., Adachi, M., Jones, F. S., Clarke, I. D., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006810 · Cited by 79 · see citing works
Yu, B., Yuan, B., Dai, J.-K., Cheng, T.-L., Xia, S.-N., He, L.-J., Yuan, Y.-T., Zhang, Y.-F., Xu, H.-T., Xu, F.-Q., et al. (2020) · Neuroscience Bulletin · doi:10.1007/s12264-020-00467-w · Cited by 58 · see citing works
Immunologic and neurodevelopmental susceptibilities of autism
Pessah, I. N., Seegal, R. F., Lein, P. J., LaSalle, J., Yee, B. K., Van De Water, J., & Berman, R. F. (2008) · NeuroToxicology · doi:10.1016/j.neuro.2008.02.006 · Cited by 51 · see citing works
Neonatal MeCP2 is important for the organization of sex differences in vasopressin expression
Forbes-Lorman, R. M., Rautio, J. J., Kurian, J. R., Auger, A. P., & Auger, C. J. (2012) · Epigenetics · doi:10.4161/epi.7.3.19265 · Cited by 43 · see citing works
MeCP2 prevents against sustained ketamine-induced synaptic depression at inhibitory synapses
Piazza, M. K., Weit, A. R., Kavalali, E. T., Neul, J. L., & Monteggia, L. M. (2025) · iScience · doi:10.1016/j.isci.2025.112485 · Cited by 3 · see citing works
- Authors
- Young, 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., & Zoghbi, H. Y.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Zoghbi, Huda Y.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-10-26
- Volume
- 102
- Issue
- 49
- Pages
- 17551-17558
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1266160
- OpenAlex
- W2168397438
- Cited by
- 484
- References
- 3
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 19 · 2023: 13 · 2022: 23 · 2021: 34 · 2020: 23 · 2019: 23 · 2018: 15 · 2017: 18 · 2016: 17 · 2015: 24 · 2014: 25 · 2013: 48 · 2012: 27
- FWCI
- 11.55
- Type
- journal article
- Language
- en
- Update notices
- correction (2006-01-19)
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Hereditary Disease Foundation
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 24064, P30HD024064, P01HD040301)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- MeCP2, Rett syndrome, RNA splicing regulation, alternative splicing, YB-1, DNA methylation, transcriptional repressor, Mecp2 knockout mice, neurodevelopmental disorders, X-linked disorders
- MeSH terms
- Animals, Exons, Humans, Models, Genetic, Protein Binding, RNA, RNA Splicing, Transcription, Genetic, Rett Syndrome, Genes, Reporter, DNA Methylation, Gene Expression Profiling, Cell Line, Tumor, Mice, Methyl-CpG-Binding Protein 2
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