HES1 is a master regulator of glucocorticoid receptor-dependent gene expression
Open accessAbstract
Hairy and enhancer of split-1 (HES1) is a basic helix-loop-helix transcription factor that is a key regulator of development and organogenesis. However, little is known about the role of HES1 after birth. Glucocorticoids, primary stress hormones that are essential for life, regulate numerous homeostatic processes that permit vertebrates to cope with physiological challenges. The molecular actions of glucocorticoids are mediated by glucocorticoid receptor-dependent regulation of nearly 25% of the genome. Here, we established a genome-wide molecular link between HES1 and glucocorticoid receptors that controls the ability of cells and animals to respond to stress. Glucocorticoid signaling rapidly and robustly silenced HES1 expression. This glucocorticoid-dependent repression of HES1 was necessary for the glucocorticoid receptor to regulate many of its target genes. Mice with conditional knockout of HES1 in the liver exhibited an expanded glucocorticoid receptor signaling profile and aberrant metabolic phenotype. Our results indicate that HES1 acts as a master repressor, the silencing of which is required for proper glucocorticoid signaling.
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.
Integrity signals
Registry
Cites
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.
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?
Through genomic mechanisms, GCs regulate the expression and protein abundance of their own regulators (i.e., HES1), and this feedback loop is mandatory for proper GC-mediated changes in gene expression.
“Finally, we note that through such genomic mechanisms, GCs regulate the expression and protein abundance of their own regulators (i.e., HES1) and that this feedback loop is mandatory for proper GC-mediated changes in gene expression (90).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [90]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 30 · Cited by 50
Research works printed but not linked: 1
- [19]Postic C Magnuson MA DNA excision in liver by an albumin-Cre transgene occurs progressively with age Genesis 26 149 2 2000 10686614
- Authors
- Revollo, J. R., Oakley, R. H., Lu, N. Z., Kadmiel, M., Gandhavadi, M., & Cidlowski, J. A.
- Affiliations
- National Institutes of Health (US)
- Northwestern University (US)
- Corresponding author
- Cidlowski, John A.
- Venue
- Science Signaling
- Published
- 2013-12-03
- Volume
- 6
- Issue
- 304
- Pages
- ra103-ra103
- ISSN
- 1937-9145 (ISSN-L)
- 1945-0877
- PMC
- PMC3997072
- OpenAlex
- W1998244294
- Cited by
- 50
- References
- 30
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 9 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 9
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Signaling (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (ZIAES090057)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- Hes1, glucocorticoid receptor, glucocorticoid signaling, transcriptional repression, bHLH transcription factors, stress response, liver, metabolic phenotypes, gene expression regulation, conditional knockout mice
- MeSH terms
- Transcription Factor HES-1, Animals, Cell Line, Gene Expression Regulation, Glucocorticoids, Receptors, Glucocorticoid, Repressor Proteins, Signal Transduction, Rats, Sprague-Dawley, Mice, Knockout, Homeodomain Proteins, Mice, Basic Helix-Loop-Helix Proteins, Genome-Wide Association Study
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
