MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription

by: Maria Chahrour, Sung Y Jung, Chad Shaw, Xiaobo Zhou, Stephen T Wong, Jun Qin, Huda Y Zoghbi

Science, Vol. 320, No. 5880. (30 May 2008), pp. 1224-1229.

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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. 10.1126/science.1153252

@article{citeulike:2847316, 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. 10.1126/science.1153252}, author = {Chahrour, Maria and Jung, Sung Y. and Shaw, Chad and Zhou, Xiaobo and Wong, Stephen T. and Qin, Jun and Zoghbi, Huda Y. }, citeulike-article-id = {2847316}, doi = {http://dx.doi.org/10.1126/science.1153252}, journal = {Science}, keywords = {epigenetics, methylation, neuroscience}, month = {May}, number = {5880}, pages = {1224--1229}, posted-at = {2008-05-30 14:23:38}, priority = {5}, title = {MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription}, url = {http://dx.doi.org/10.1126/science.1153252}, volume = {320}, year = {2008} }

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TY - JOUR ID - citeulike:2847316 L3 - citeulike-article-id:2847316 TI - MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription JF - Science VL - 320 IS - 5880 SP - 1224 EP - 1229 N2 - 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. 10.1126/science.1153252 KW - epigenetics KW - methylation KW - neuroscience AU - Chahrour, Maria AU - Jung, Sung AU - Shaw, Chad AU - Zhou, Xiaobo AU - Wong, Stephen AU - Qin, Jun AU - Zoghbi, Huda PY - 2008/05/30/ UR - http://dx.doi.org/10.1126/science.1153252 ER -

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