Cited by 104Epigenetics and DNA MethylationGenomics and Chromatin DynamicsGenetic Syndromes and Imprinting

Highly individual methylation patterns of alternative glucocorticoid receptor promoters suggest individualized epigenetic regulatory mechanisms

Open access
Turner, J. D., Pelascini, L. P. L., Macedo, J. A., Muller, C. P.·2008·Nucleic Acids Research

Abstract

The transcription start sites (TSS) and promoters of many genes are located in upstream CpG islands. Methylation within such islands is known for both imprinted and oncogenes, although poorly studied for other genes, especially those with complex CpG islands containing multiple first exons and promoters. The glucocorticoid receptor (GR) CpG island contains seven alternative first exons and their promoters. Here we show for the five GR promoters activated in PBMCs that methylation patterns are highly variable between individuals. The majority of positions were methylated at levels >25% in at least one donor affecting each promoter and TSS. We also examined the evolutionarily conserved transcription factor binding sites (TFBS) using an improved in silico phylogenetic footprinting technique. The majority of these contain methylatable CpG sites, suggesting that methylation may orchestrates alternative first exon usage, silencing and controlling tissue-specific expression. The heterogeneity observed may reflect epigenetic mechanisms of GR fine tuning, programmed by early life environment and events. With 78% of evolutionarily conserved alternative first exons falling into such complex CpG islands, their internal structure and epigenetic modifications are bound to be biologically important, and may be a common transcriptional control mechanism used throughout many phyla.

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 · 10.1093/nar/gkn897

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?

  • Stress or trauma was correlated with higher methylation of exon 1F of NR3C1, the homolog of exon 17 in the rat.

    “The results of these studies consistently demonstrated that stress or trauma was correlated with higher methylation of exon 1F of NR3C1, which is the homolog of exon 17 in the rat (Turner, Pelascini, Macedo, & Muller, 2008).”

    From Associations Between Early Life Stress and Gene Methylation in Children (2015) · cites this paper as Turner et al., 2008

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
Turner, J. D., Pelascini, L. P. L., Macedo, J. A., & Muller, C. P.
Affiliations
Laboratoire National de Santé (LU)
Corresponding author
Muller, C. P.
Venue
Nucleic Acids Research
Published
2008-11-12
Volume
36
Issue
22
Pages
7207-7218
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
OpenAlex
W2169090691
Cited by
104
References
56
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 2 · 2018: 6 · 2017: 2 · 2016: 5 · 2015: 12 · 2014: 13 · 2013: 10 · 2012: 19
FWCI
3.29
Type
journal article
Language
en
Open access
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
Deutsche Forschungsgemeinschaft (GRK 1389/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
Keywords
glucocorticoid receptor, alternative first exons, promoter methylation, CpG islands, transcription start sites, transcription factor binding sites, phylogenetic footprinting, tissue-specific gene expression, epigenetic regulation, peripheral blood mononuclear cells
MeSH terms
Adult, Aged, Animals, Binding Sites, Cattle, Female, Humans, Male, Middle Aged, Phylogeny, Promoter Regions, Genetic, Receptors, Glucocorticoid, Transcription Factors, CpG Islands, DNA Methylation, Genomics, Transcription Initiation Site, Epigenesis, Genetic, Mice, Rats

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