Thyroid hormone-regulated gene expression in juvenile mouse liver: identification of thyroid response elements using microarray profiling and in silico analyses

Paquette, Martin A; Dong, Hongyan; Gagné, Rémi; Williams, Andrew; Malowany, Morie; Wade, Mike G; Yauk, Carole L

doi:10.1186/1471-2164-12-634

Cited by 24Thyroid Disorders and TreatmentsEffects and risks of endocrine disrupting chemicalsEstrogen and related hormone effects

Thyroid hormone-regulated gene expression in juvenile mouse liver: identification of thyroid response elements using microarray profiling and in silico analyses

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Paquette, Martin A, Dong, Hongyan, Gagné, Rémi, Williams, Andrew, Malowany, Morie, Wade, Mike G, Yauk, Carole L·2011·BMC Genomics

DOI 10.1186/1471-2164-12-634PMC PMC3340398

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Abstract

Background: Disruption of thyroid hormone signalling can alter growth, development and energy metabolism. Thyroid hormones exert their effects through interactions with thyroid receptors that directly bind thyroid response elements and can alter transcriptional activity of target genes. The effects of short-term thyroid hormone perturbation on hepatic mRNA transcription in juvenile mice were evaluated, with the goal of identifying genes containing active thyroid response elements. Thyroid hormone disruption was induced from postnatal day 12 to 15 by adding goitrogens to dams' drinking water (hypothyroid). A subgroup of thyroid hormone-disrupted pups received intraperitoneal injections of replacement thyroid hormones four hours prior to sacrifice (replacement). An additional group received only thyroid hormones four hours prior to sacrifice (hyperthyroid). Hepatic mRNA was extracted and hybridized to Agilent mouse microarrays. Results: Transcriptional profiling enabled the identification of 28 genes that appeared to be under direct thyroid hormone-regulation. The regulatory regions of the genome adjacent to these genes were examined for half-site sequences that resemble known thyroid response elements. A bioinformatics search identified 33 thyroid response elements in the promoter regions of 13 different genes thought to be directly regulated by thyroid hormones. Thyroid response elements found in the promoter regions of Tor1a, 2310003H01Rik, Hect3d and Slc25a45 were further validated by confirming that the thyroid receptor is associated with these sequences in vivo and that it can bind directly to these sequences in vitro. Three different arrangements of thyroid response elements were identified. Some of these thyroid response elements were located far up-stream (> 7 kb) of the transcription start site of the regulated gene. Conclusions: Transcriptional profiling of thyroid hormone disrupted animals coupled with a novel bioinformatics search revealed new thyroid response elements associated with genes previously unknown to be responsive to thyroid hormone. The work provides insight into thyroid response element sequence motif characteristics.

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Dio1 and Hectd3 are previously identified THRB hepatic target genes.
“stimulation of the Dio1 and Hectd3 gene expression, which are previously identified THRB hepatic target genes (Fig 5B; Paquette et al, 2011).”
From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Paquette et al, 2011
The Results (ChIP-PCR Analysis; page unavailable) report TRβ-1 binding at a Hectd3 promoter response element, supporting Hectd3 as a hepatic TRβ target. The Discussion (page unavailable) identifies Dio1 as responsive to thyroid hormone in liver, but says it did not meet this study’s criteria for potentially direct regulation; the paper does not establish Dio1 as a TRβ hepatic target. (LLM, conf=0.88)
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Authors: Paquette, M. A., Dong, H., Gagné, R., Williams, A., Malowany, M., Wade, M. G., & Yauk, C. L.
Affiliations: Health Canada (CA)
Corresponding author: Yauk, Carole L
ORCID: Dong, Hongyan
Williams, Andrew
Yauk, Carole L
Venue: BMC Genomics
Publisher: Springer Science and Business Media LLC
Published: 2011-12
Volume: 12
Issue: 1
Pages: 634-634
ISSN: 1471-2164 (ISSN-L)
DOI: 10.1186/1471-2164-12-634
PMC: PMC3340398
OpenAlex: W2081921666
Cited by: 24
References: 65
Citations by year: 2026: 1 · 2025: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 6 · 2013: 3 · 2012: 1
FWCI: 2.62
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
www.springer.com/tdm (unspecified)
Locations: BMC Genomics (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Health Canada
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords: thyroid hormones, thyroid response element, thyroid hormone receptor, hepatic gene expression, thyroid hormone replacement, hyperthyroidism, promoter analysis, transcriptional regulation
MeSH terms: Animals, Base Sequence, Female, Gene Expression Regulation, Liver, Male, Mice, Inbred C57BL, Promoter Regions, Genetic, Receptors, Thyroid Hormone, RNA, Messenger, Thyroid Gland, Thyroid Hormones, Transcription, Genetic, Signal Transduction, Transcriptional Activation, Sequence Analysis, DNA, Molecular Chaperones, Response Elements, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Ubiquitin-Protein Ligases, Mice

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Thyroid hormone-regulated gene expression in juvenile mouse liver: identification of thyroid response elements using microarray profiling and in silico analyses

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