The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription
Open accessAbstract
Mutations in the gene encoding the transcriptional repressor methyl-CpG binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome. Loss of function as well as increased dosage of the MECP2 gene cause a host of neuropsychiatric disorders. To explore the molecular mechanism(s) underlying these disorders, we examined gene expression patterns in the hypothalamus of mice that either lack or overexpress MeCP2. In both models, MeCP2 dysfunction induced changes in the expression levels of thousands of genes, but unexpectedly the majority of genes (∼85%) appeared to be activated by MeCP2. We selected six genes and confirmed that MeCP2 binds to their promoters. Furthermore, we showed that MeCP2 associates with the transcriptional activator CREB1 at the promoter of an activated target but not a repressed target. These studies suggest that MeCP2 regulates the expression of a wide range of genes in the hypothalamus and that it can function as both an activator and a repressor of transcription.
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“While Mecp2 mutant mice are an excellent model for RTT, elimination of MeCP2 affects the expression of a profound number of pathways in the CNS, making it difficult to pinpoint which ones play a key role in pathology [77,89,90].”
From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [77]
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“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 [77]
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“Altogether, multiple studies suggest that genes can be activated or repressed by MeCP2, depending upon the cellular context [77,89,90], suggesting that MeCP2 may be defined as a transcriptional modulator.”
From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [77]
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“These data are consistent with another study showing that MeCP2 binding to methylated DNA has a biphasic impact on transcription.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [123]
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Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2
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Research works printed but not linked: 3
- C. L. Martinet al., Am. J. Med. Genet. B. Neuropsychiatr. Genet.144, 869 (2007).
- H. Caldeira Araujoet al., Am. J. Med. Genet. A.133, 122 (2005).
- We thank members of the Zoghbi laboratory for their thoughtful comments Z. Yin for technical assistance M. Shinawi and A. Tawil for technical advice Y. Klisch for the art work and J. Lim J. Neul and M. Greenberg for reagents. The Baylor College of Medicine Microarray Core Facility performed the microarray experiments. This work was funded by NIH/National Institute of Neurological Disorders and Stroke grant NS057819 (H.Z.) National Institute of Child Health and Human Development Mental Retardation and Developmental Disabilities Research Center HD024064 (H.Z.) the International Rett Syndrome Foundation and the Simons Foundation. H.Z. is a Howard Hughes Medical Institute investigator. The microarray data have been deposited in the National Center for Biotechnology Information Gene Expression Omnibus (GEO) (www.ncbi.nlm.nih.gov/geo) and are accessible through GEO Series accession number GSE11150.
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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
Metadata
- Authors
- Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T. C., Qin, J., & Zoghbi, H. Y.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Zoghbi, Huda Y.
- Venue
- Science
- Published
- 2008-05-30
- Volume
- 320
- Issue
- 5880
- Pages
- 1224-1229
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2443785
- OpenAlex
- W2039276157
- Cited by
- 1,823
- References
- 22
- Citations by year
- 2026: 53 · 2025: 55 · 2024: 76 · 2023: 67 · 2022: 84 · 2021: 95 · 2020: 96 · 2019: 90 · 2018: 69 · 2017: 131 · 2016: 133 · 2015: 113 · 2014: 131 · 2013: 153 · 2012: 128
- FWCI
- 66.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (NS057819, R01NS057819)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 024064, P30HD024064)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- MeCP2, Rett syndrome, transcriptional repression, transcriptional activation, CREB1, promoter binding, hypothalamus, gene expression profiling, neuropsychiatric disorders, neurodevelopmental disorders
- MeSH terms
- Animals, Disease Models, Animal, Gene Expression Regulation, Hypothalamic Diseases, Hypothalamus, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Nervous System Diseases, Protein Binding, Repressor Proteins, Transcription Factors, Rett Syndrome, Transcriptional Activation, Cyclic AMP Response Element-Binding Protein, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Mice, Methyl-CpG-Binding Protein 2
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