Vol 4: Increased binding of MeCP2 to the GAD1 and RELN promoters may be mediated by an enrichment of 5-hmC in autism spectrum disorder ASD cerebellum.Report as inadecuate



 Vol 4: Increased binding of MeCP2 to the GAD1 and RELN promoters may be mediated by an enrichment of 5-hmC in autism spectrum disorder ASD cerebellum.


Vol 4: Increased binding of MeCP2 to the GAD1 and RELN promoters may be mediated by an enrichment of 5-hmC in autism spectrum disorder ASD cerebellum. - Download this document for free, or read online. Document in PDF available to download.

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This article is from Translational Psychiatry, volume 4.AbstractAutism spectrum disorder ASD is a neurodevelopmental disorder characterized by symptoms related to altered social interactions-communication and restricted and repetitive behaviors. In addition to genetic risk, epigenetic mechanisms which include DNA methylation-demethylation are thought to be important in the etiopathogenesis of ASD. We studied epigenetic mechanisms underlying the transcriptional regulation of candidate genes in cerebella of ASD patients, including the binding of MeCP2 methyl CpG binding protein-2 to the glutamic acid decarboxylase 67 GAD1, glutamic acid decarboxylase 65 GAD2, and Reelin RELN promoters and gene bodies. Moreover, we performed methyl DNA immunoprecipitation MeDIP and hydroxymethyl DNA immunoprecipitation hMeDIP to measure total 5-methylcytosine 5-mC and 5-hydroxymethylcytosine 5-hmC in the same regions of these genes. The enrichment of 5-hmC and decrease in 5-mC at the GAD1 or RELN promoters detected by 5-hmC and 5-mC antibodies was confirmed by Tet-assisted bisulfite TAB pyrosequencing. The results showed a marked and significant increase in MeCP2 binding to the promoter regions of GAD1 and RELN, but not to the corresponding gene body regions in cerebellar cortex of ASD patients. Moreover, we detected a significant increase in TET1 expression and an enrichment in the level of 5-hmC, but not 5-mC, at the promoters of GAD1 and RELN in ASD when compared with CON. Moreover, there was increased TET1 binding to these promoter regions. These data are consistent with the hypothesis that an increase of 5-hmC relative to 5-mC at specific gene domains enhances the binding of MeCP2 to 5-hmC and reduces expression of the corresponding target genes in ASD cerebella.



Author: Zhubi, A; Chen, Y; Dong, E; Cook, E H; Guidotti, A; Grayson, D R

Source: https://archive.org/







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