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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MYC deregulates TET1 and TET2 expression to control global DNA (hydroxy)methylation and gene expression to maintain a neoplastic phenotype in T-ALL
TL;DR: The finding that MYC directly deregulates the expression of TET1 and TET2 in T-ALL provides novel evidence thatMYC controls DNA (hydroxy)methylation in a genome-wide fashion, and reveals a coordinated interplay between the components of the DNA (de)methylating machinery that contribute to MYC-driven tumor maintenance.
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Preterm Birth and the Risk of Neurodevelopmental Disorders - Is There a Role for Epigenetic Dysregulation?
TL;DR: The potential role of epigenetic dysregulation in mediating the effects of PTB on neurodevelopmental outcome is discussed, with specific emphasis on DNA methylation and the α-ketoglutarate dependent dioxygenase family of enzymes.
Journal ArticleDOI
Subtraction-free and bisulfite-free specific sequencing of 5-methylcytosine and its oxidized derivatives at base resolution.
Yibin Liu,Zhiyuan Hu,Jingfei Cheng,Jingfei Cheng,Paulina Siejka-Zielińska,Paulina Siejka-Zielińska,Jinfeng Chen,Jinfeng Chen,Masato Inoue,Masato Inoue,Ahmed Ashour Ahmed,Chun-Xiao Song,Chun-Xiao Song +12 more
TL;DR: It is demonstrated that two sister methods, TAPSβ and chemical-assisted pyridine borane sequencing (CAPS), can be effectively used for subtraction-free and specific whole-genome sequencing of 5mC and 5hmC, respectively.
Journal ArticleDOI
Loss of 5-hydroxymethylcytosine and intratumoral heterogeneity as an epigenomic hallmark of glioblastoma
Theo F. J. Kraus,Gesa Kolck,Andrea Greiner,Katharina Schierl,Virginie Guibourt,Hans A. Kretzschmar +5 more
TL;DR: The data emphasize that GBMs show a disturbed hydroxymethylome that is disrupted by IDH1 independent pathways, and that loss of 5hmC shows astonishing intratumoral heterogeneity.
Journal ArticleDOI
Sex-specific hippocampal 5-hydroxymethylcytosine is disrupted in response to acute stress.
Ligia A. Papale,Sisi Li,Andy Madrid,Qi Zhang,Li Chen,Pankaj Chopra,Peng Jin,Sunduz Keles,Reid S. Alisch +8 more
TL;DR: Together, the alterations in 5hmC presented here provide a possible molecular mechanism for the adaptive sex-specific response to stress that may augment the design of novel therapeutic agents that will have optimal effectiveness in each sex.
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Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
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