MeCP2, a key contributor to neurological disease, activates and represses transcription

Maria Chahrour, Yun Jung Sung, Chad Shaw, Xiaobo Zhou, Stephen T.C. Wong, Jun Qin, Huda Y. Zoghbi

Research output: Contribution to journalArticle

1085 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1224-1229
Number of pages6
JournalScience
Volume320
Issue number5880
DOIs
StatePublished - May 30 2008

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Methyl-CpG-Binding Protein 2
Genes
Hypothalamus
Rett Syndrome
Gene Dosage
Gene Expression
Mutation

ASJC Scopus subject areas

  • General

Cite this

Chahrour, M., Sung, Y. J., Shaw, C., Zhou, X., Wong, S. T. C., Qin, J., & Zoghbi, H. Y. (2008). MeCP2, a key contributor to neurological disease, activates and represses transcription. Science, 320(5880), 1224-1229. https://doi.org/10.1126/science.1153252

MeCP2, a key contributor to neurological disease, activates and represses transcription. / Chahrour, Maria; Sung, Yun Jung; Shaw, Chad; Zhou, Xiaobo; Wong, Stephen T.C.; Qin, Jun; Zoghbi, Huda Y.

In: Science, Vol. 320, No. 5880, 30.05.2008, p. 1224-1229.

Research output: Contribution to journalArticle

Chahrour, M, Sung, YJ, Shaw, C, Zhou, X, Wong, STC, Qin, J & Zoghbi, HY 2008, 'MeCP2, a key contributor to neurological disease, activates and represses transcription', Science, vol. 320, no. 5880, pp. 1224-1229. https://doi.org/10.1126/science.1153252
Chahrour, Maria ; Sung, Yun Jung ; Shaw, Chad ; Zhou, Xiaobo ; Wong, Stephen T.C. ; Qin, Jun ; Zoghbi, Huda Y. / MeCP2, a key contributor to neurological disease, activates and represses transcription. In: Science. 2008 ; Vol. 320, No. 5880. pp. 1224-1229.
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