Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 (approximately 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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PMID:MeCP2, a key contributor to neurological disease, activates and represses transcription. 1851 80

The X-chromosomal MECP2/Mecp2 gene encodes methyl-CpG-binding protein 2, a transcriptional activator and repressor regulating many other genes. We discovered in male FVB/N mice that mild (~50%) transgenic overexpression of Mecp2 enhances aggression. Surprisingly, when the same transgene was expressed in C57BL/6N mice, transgenics showed reduced aggression and social interaction. This suggests that Mecp2 modulates aggressive social behavior. To test this hypothesis in humans, we performed a phenotype-based genetic association study (PGAS) in >1000 schizophrenic individuals. We found MECP2 SNPs rs2239464 (G/A) and rs2734647 (C/T; 3'UTR) associated with aggression, with the G and C carriers, respectively, being more aggressive. This finding was replicated in an independent schizophrenia cohort. Allele-specific MECP2 mRNA expression differs in peripheral blood mononuclear cells by ~50% (rs2734647: C > T). Notably, the brain-expressed, species-conserved miR-511 binds to MECP2 3'UTR only in T carriers, thereby suppressing gene expression. To conclude, subtle MECP2/Mecp2 expression alterations impact aggression. While the mouse data provides evidence of an interaction between genetic background and mild Mecp2 overexpression, the human data convey means by which genetic variation affects MECP2 expression and behavior.
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PMID:Mild expression differences of MECP2 influencing aggressive social behavior. 2464 99

It has been a long trip from 1992, the year of the discovery of MECP2, to the present day. What is surprising is that some of the pivotal roles of MeCP2 were already postulated at that time, such as repression of inappropriate expression from repetitive elements and the regulation of pericentric heterochromatin condensation. However, MeCP2 performs many more functions. MeCP2 is a reader of epigenetic information contained in methylated (and hydroxymethylated) DNA, moving from the 'classical' CpG doublet to the more complex view addressed by the non-CpG methylation, which is a feature of the postnatal brain. MECP2 is a transcriptional repressor, although when it forms complexes with the appropriate molecules, it can become a transcriptional activator. For all of these aspects, Rett syndrome, which is caused by MECP2 mutations, is considered a paradigmatic example of a 'chromatin disorder'. Even if the hunt for bona-fide MECP2 target genes is far from concluded today, the role of MeCP2 in the maintenance of chromatin architecture appears to be clearly established. Taking a cue from the non-scientific literature, we can firmly attest that MeCP2 is a player with 'a great future behind it'*.*V. Gassmann 'Un grande avvenire dietro le spalle'. TEA Eds.
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PMID:MECP2, a multi-talented modulator of chromatin architecture. 2729 83