MeCP2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system
TLDR
In this paper, a quantitative, genome-wide analysis of 5hmC, 5-methylcytosine (5mC), and gene expression in differentiated CNS cell types in vivo is presented.Abstract:
SUMMARY The high level of 5-hydroxymethylcytosine (5hmC) present in neuronal genomes suggests that mechanisms interpreting 5hmC in the CNS may differ from those present in embryonic stem cells. Here, we present quantitative, genome-wide analysis of 5hmC, 5-methylcytosine (5mC), and gene expression in differentiated CNS cell types in vivo. We report that 5hmC is enriched in active genes and that, surprisingly, strong depletion of 5mC is observed over these regions. The contribution of these epigenetic marks to gene expression depends critically on cell type. We identify methyl-CpG-binding protein 2 (MeCP2) as the major 5hmC-binding protein in the brain and demonstrate that MeCP2 binds 5hmC- and 5mC-containing DNA with similar high affinities. The Rett-syndrome-causing mutation R133C preferentially inhibits 5hmC binding. These findings support a model in which 5hmC and MeCP2 constitute a cell-specific epigenetic mechanism for regulation of chromatin structure and gene expression.read more
Citations
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MeCP2 facilitates breast cancer growth via promoting ubiquitination-mediated P53 degradation by inhibiting RPL5/RPL11 transcription.
Dongdong Tong,Jing Zhang,Xiaofei Wang,Qian Li,Li Ying Liu,Juan Yang,Bo Guo,Lei Ni,Lingyu Zhao,Chen Huang +9 more
TL;DR: It is demonstrated that MeCP2 promotes breast cancer cell proliferation and inhibits apoptosis through suppressing RPL11 and RPL5 transcription by binding to their promoter regions and suppressing ubiquitination-mediated P53 degradation through direct binding to MDM2.
Journal ArticleDOI
DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells.
Sarah J. Hainer,Kurtis N. McCannell,Jun Yu,Ly-Sha Ee,Lihua Julie Zhu,Oliver J. Rando,Thomas G. Fazzio +6 more
TL;DR: It is shown that chromatin localization of Mbd2 and Mbd3 is highly overlapping and, unexpectedly, it is found Mbd 2 and MBD3 are interdependent for chromatin association, revealing an interdependent regulatory mechanism mediated by the DNA methylation machinery and its readers.
Journal ArticleDOI
Diverse and dynamic DNA modifications in brain and diseases
TL;DR: This review highlights recent advances in the understanding of the methylome's functionality and covers potential new roles for DNA methylation, their readers, writers, and erasers and outlines the gaps in knowledge that will likely be filled through the widespread use of newer technologies that provide greater resolution into how individual cell types are affected by disease.
Journal ArticleDOI
Elevated 5hmC levels characterize DNA of the cerebellum in Parkinson's disease.
TL;DR: The distinct epigenetic profile identified in cerebellar DNA of Parkinson’s disease patients raises the question whether elevated 5-hydroxymethylcytosine levels are a driver or a consequence of Parkinson's disease.
Journal ArticleDOI
TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice.
Sarah Moyon,Rebecca Frawley,Damien Marechal,Dennis Huang,Katy Lh Marshall-Phelps,Linde Kegel,Sunniva M. K. Bøstrand,Boguslawa Sadowski,Boguslawa Sadowski,Yong-hui Jiang,David A. Lyons,Wiebke Möbius,Wiebke Möbius,Patrizia Casaccia +13 more
TL;DR: In this article, the authors identify DNA hydroxymethylation, catalyzed by the TET enzyme TET1, as necessary for myelin repair in young adults and defective in old mice.
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Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
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TL;DR: This study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.