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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Journal ArticleDOI
Global Impairment of Immediate-Early Genes Expression in Rett Syndrome Models and Patients Linked to Myelination Defects
Paolo Petazzi,Olga C. Jorge-Torres,Antonio Gomez,Iolanda Scognamiglio,Jordi Serra-Musach,Angelika Merkel,Daniela Grases,Clara Xiol,Maria del Mar O’Callaghan,Judith Armstrong,Manel Esteller,Sonia Guil +11 more
TL;DR: In this paper , the authors used RNA-sequencing analysis to find several immediate-early genes (IEGs, key mediators of activity-dependent responses) directly bound by MeCP2 at the chromatin level and upregulated in the hippocampus and prefrontal cortex of the Mecp2-KO mouse.
Journal ArticleDOI
Altered Brain Expression of DNA Methylation and Hydroxymethylation Epigenetic Enzymes in a Rat Model of Neuropathic Pain
TL;DR: In this article , the functional role of TET1-3 and DNMT1/3a genes in neuropathic pain in several brain areas was evaluated. But no statistically significant changes in expression were observed with DNMT3a.
Journal ArticleDOI
Tet Enzymes-Mediated DNA 5hmC Modification in Cerebral Ischemic and Hemorrhagic Injury
TL;DR: It is suggested that 5hmC may serve as a biomarker or therapeutic target for the treatment of stroke and summarized the possible therapeutic prospects of5hmC in stroke.
Dissertation
Developing novel therapeutic strategies for Rett syndrome
TL;DR: A newly created peripheral knock-out (KO) mouse model, in which Mecp2 transcription is silenced in peripheral tissues but selectively reactivated in the cells of the nervous system, was comprehensively phenotyped in order to determine the role of peripheral MeCP2 in RTT.
Journal ArticleDOI
In silico structural analysis of sequences containing 5-hydroxymethylcytosine reveals its potential as binding regulator for development, ageing and cancer-related transcription factors.
TL;DR: It is concluded that cytosine hydroxymethylation could play a role in the recognition of sequences with G-quadruplexes/palindromes by forming epigenetically regulated DNA ‘springs’ and governing expansions or compressions recognized by different transcription factors or stabilizing nucleosomes.
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