Cited by 943Epigenetics and DNA MethylationGenetics and Neurodevelopmental DisordersGenomics and Chromatin Dynamics

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

Open access
Mellén, Marian, Ayata, Pinar, Dewell, Scott, Kriaucionis, Skirmantas, Heintz, Nathaniel·2012·Cell

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cell.2012.11.022

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 5hmC in the nervous system is associated with actively transcribed genes and recognized by MeCP2, which is inactivated in Rett syndrome.

    “5hmC in the nervous system is associated with actively transcribed genes and is recognized by the histone-reader protein MeCP2, which is mutationally inactivated in the neurological disorder of Rett syndrome (Mellén et al., 2012).”

    From Influence of Metabolism on Epigenetics and Disease (2013) · cites this paper as Mellén et al., 2012

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Mellén, M., Ayata, P., Dewell, S., Kriaucionis, S., & Heintz, N.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Rockefeller University (US)
Corresponding author
Heintz, Nathaniel
Venue
Cell
Publisher
Elsevier BV
Published
2012-12
Volume
151
Issue
7
Pages
1417-1430
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2113486281
Cited by
943
References
56
Citations by year
2026: 27 · 2025: 35 · 2024: 45 · 2023: 38 · 2022: 45 · 2021: 46 · 2020: 60 · 2019: 60 · 2018: 70 · 2017: 97 · 2016: 105 · 2015: 94 · 2014: 121 · 2013: 93
FWCI
39.63
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of Mental Health (P50MH090963, MH090963)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
5-hydroxymethylcytosine, 5-methylcytosine, MeCP2, Rett syndrome, DNA methylation, epigenetic regulation, gene expression, chromatin accessibility, neuronal cell types, brain, chromatin structure
MeSH terms
Animals, Cerebellum, Chromatin, Cytosine, Humans, Neuroglia, Neurons, Purkinje Cells, Rett Syndrome, Mice, Knockout, Epigenesis, Genetic, 5-Methylcytosine, Mice, Methyl-CpG-Binding Protein 2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review