MeCP2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system

By M. Mellén, Pinar Ayata, Scott B. Dewell, Skirmantas Kriaucionis, N. Heintz. Epigenetics & Chromatin, 2013

925 citations recorded by the source corpus.

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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/dbd229faeba0773b70125cd8639762db886c2875

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Citations in the corpus

Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives. (2013, neutral): “Uhrf1 and MeCP2 are known to bind both mC and hmC, although MeCP2 clearly binds with a higher affinity to mC compared to hmC (Frauer et al., 2011; Hashimoto et al., 2012; Mellén et al., 2012).”
Interpreting thelanguage of histone and DNA modifications (2014, background): “Recent studies have also suggested thatMBD proteins are capable of reading 5hmC [139,172].”
Transcriptional Addiction in Cancer (2017, neutral): “, meCP2), thereby influencing transcriptional regulation (Baubec et al., 2013; Liu et al., 2016a; Mellen et al., 2012).”
Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain (2015, neutral): “Neuronal Diversity in the”
Global Epigenomic Reconfiguration During Mammalian Brain Development (2013, background): “hmC accumulates during early postnatal brain development in mice (31, 32), becoming enriched in highly expressed genes (33).”
Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions (2014, positive): “…investigated, including mouse/human ESCs (Ficz et al., 2011; Pastor et al., 2011; Szulwach et al., 2011a; Williams et al., 2011; Wu et al., 2011a; Xu et al., 2011b) (Rest in Figure 3B), mouse cerebellum (Mellén et al., 2012; Song et al., 2011), and mouse/human fontal cortex (Lister et al., 2013).”
Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis (2014, background): “…during active demethylation of the DNA, especially TET1-mediated cytosine hydroxymethylation, gained interest as they seem to have regulatory function that differs from the simple absence of methylation (Kaas et al. 2013; Mellén et al. 2012 p. 2; Rudenko et al. 2013; Szulwach et al. 2011).”