Evidence map›Paper›PMID 25866873›Full record

ArticleMolecular endocrinology (Baltimore, Md.)2015

Deciphering the regulatory logic of an ancient, ultraconserved nuclear receptor enhancer module.

Pia D Bagamasbad, Ronald M Bonett, Laurent Sachs, Nicolas Buisine, Samhitha Raj, Joseph R Knoedler, Yasuhiro Kyono, Yijun Ruan, Xiaoan Ruan, Robert J Denver

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 83 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. An Atlas of Thyroid Hormone Receptors' Target Genes in Mouse Tissues.International journal of molecular sciences · 2022
    Article
  7. Review
  8. Dioxin Disrupts Thyroid Hormone and Glucocorticoid Induction of klf9, a Master Regulator of Frog Metamorphosis.Toxicological sciences : an official journal of the Society of Toxicology · 2022
    Article
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  11. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Pia D BagamasbadDepartment of Molecular, Cellular and Developmental Biology (P.D.B., S.R., R.J.D.), University of Michigan, Ann Arbor, Michigan 48109; Department of Biological Science (R.M.B.), The University of Tulsa, Tulsa, Oklahoma 74104; Unité Mixte de Recherche 7221 (L.S., N.B.), Muséum National d'Histoire Naturelle, Centre Nationale de Recherche Scientifique, CP32 Paris, France; Neuroscience Graduate Program (J.R.K., Y.K., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109; Genome Institute of Singapore (Y.R., X.R.), 138672 Singapore; The Jackson Laboratory of Genomic Medicine (Y.R., X.R.), Farmington, Connecticut 06030; and Department of Genetics and Developmental Biology (Y.R., X.R.), University of Connecticut, Storrs, Connecticut 06269.
Ronald M BonettDepartment of Molecular, Cellular and Developmental Biology (P.D.B., S.R., R.J.D.), University of Michigan, Ann Arbor, Michigan 48109; Department of Biological Science (R.M.B.), The University of Tulsa, Tulsa, Oklahoma 74104; Unité Mixte de Recherche 7221 (L.S., N.B.), Muséum National d'Histoire Naturelle, Centre Nationale de Recherche Scientifique, CP32 Paris, France; Neuroscience Graduate Program (J.R.K., Y.K., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109; Genome Institute of Singapore (Y.R., X.R.), 138672 Singapore; The Jackson Laboratory of Genomic Medicine (Y.R., X.R.), Farmington, Connecticut 06030; and Department of Genetics and Developmental Biology (Y.R., X.R.), University of Connecticut, Storrs, Connecticut 06269.
Laurent SachsDepartment of Molecular, Cellular and Developmental Biology (P.D.B., S.R., R.J.D.), University of Michigan, Ann Arbor, Michigan 48109; Department of Biological Science (R.M.B.), The University of Tulsa, Tulsa, Oklahoma 74104; Unité Mixte de Recherche 7221 (L.S., N.B.), Muséum National d'Histoire Naturelle, Centre Nationale de Recherche Scientifique, CP32 Paris, France; Neuroscience Graduate Program (J.R.K., Y.K., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109; Genome Institute of Singapore (Y.R., X.R.), 138672 Singapore; The Jackson Laboratory of Genomic Medicine (Y.R., X.R.), Farmington, Connecticut 06030; and Department of Genetics and Developmental Biology (Y.R., X.R.), University of Connecticut, Storrs, Connecticut 06269.
Nicolas BuisineDepartment of Molecular, Cellular and Developmental Biology (P.D.B., S.R., R.J.D.), University of Michigan, Ann Arbor, Michigan 48109; Department of Biological Science (R.M.B.), The University of Tulsa, Tulsa, Oklahoma 74104; Unité Mixte de Recherche 7221 (L.S., N.B.), Muséum National d'Histoire Naturelle, Centre Nationale de Recherche Scientifique, CP32 Paris, France; Neuroscience Graduate Program (J.R.K., Y.K., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109; Genome Institute of Singapore (Y.R., X.R.), 138672 Singapore; The Jackson Laboratory of Genomic Medicine (Y.R., X.R.), Farmington, Connecticut 06030; and Department of Genetics and Developmental Biology (Y.R., X.R.), University of Connecticut, Storrs, Connecticut 06269.
Samhitha RajDepartment of Molecular, Cellular and Developmental Biology (P.D.B., S.R., R.J.D.), University of Michigan, Ann Arbor, Michigan 48109; Department of Biological Science (R.M.B.), The University of Tulsa, Tulsa, Oklahoma 74104; Unité Mixte de Recherche 7221 (L.S., N.B.), Muséum National d'Histoire Naturelle, Centre Nationale de Recherche Scientifique, CP32 Paris, France; Neuroscience Graduate Program (J.R.K., Y.K., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109; Genome Institute of Singapore (Y.R., X.R.), 138672 Singapore; The Jackson Laboratory of Genomic Medicine (Y.R., X.R.), Farmington, Connecticut 06030; and Department of Genetics and Developmental Biology (Y.R., X.R.), University of Connecticut, Storrs, Connecticut 06269.
Joseph R KnoedlerDepartment of Molecular, Cellular and Developmental Biology (P.D.B., S.R., R.J.D.), University of Michigan, Ann Arbor, Michigan 48109; Department of Biological Science (R.M.B.), The University of Tulsa, Tulsa, Oklahoma 74104; Unité Mixte de Recherche 7221 (L.S., N.B.), Muséum National d'Histoire Naturelle, Centre Nationale de Recherche Scientifique, CP32 Paris, France; Neuroscience Graduate Program (J.R.K., Y.K., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109; Genome Institute of Singapore (Y.R., X.R.), 138672 Singapore; The Jackson Laboratory of Genomic Medicine (Y.R., X.R.), Farmington, Connecticut 06030; and Department of Genetics and Developmental Biology (Y.R., X.R.), University of Connecticut, Storrs, Connecticut 06269.
Yasuhiro KyonoDepartment of Molecular, Cellular and Developmental Biology (P.D.B., S.R., R.J.D.), University of Michigan, Ann Arbor, Michigan 48109; Department of Biological Science (R.M.B.), The University of Tulsa, Tulsa, Oklahoma 74104; Unité Mixte de Recherche 7221 (L.S., N.B.), Muséum National d'Histoire Naturelle, Centre Nationale de Recherche Scientifique, CP32 Paris, France; Neuroscience Graduate Program (J.R.K., Y.K., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109; Genome Institute of Singapore (Y.R., X.R.), 138672 Singapore; The Jackson Laboratory of Genomic Medicine (Y.R., X.R.), Farmington, Connecticut 06030; and Department of Genetics and Developmental Biology (Y.R., X.R.), University of Connecticut, Storrs, Connecticut 06269.
Yijun RuanDepartment of Molecular, Cellular and Developmental Biology (P.D.B., S.R., R.J.D.), University of Michigan, Ann Arbor, Michigan 48109; Department of Biological Science (R.M.B.), The University of Tulsa, Tulsa, Oklahoma 74104; Unité Mixte de Recherche 7221 (L.S., N.B.), Muséum National d'Histoire Naturelle, Centre Nationale de Recherche Scientifique, CP32 Paris, France; Neuroscience Graduate Program (J.R.K., Y.K., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109; Genome Institute of Singapore (Y.R., X.R.), 138672 Singapore; The Jackson Laboratory of Genomic Medicine (Y.R., X.R.), Farmington, Connecticut 06030; and Department of Genetics and Developmental Biology (Y.R., X.R.), University of Connecticut, Storrs, Connecticut 06269.
Xiaoan RuanDepartment of Molecular, Cellular and Developmental Biology (P.D.B., S.R., R.J.D.), University of Michigan, Ann Arbor, Michigan 48109; Department of Biological Science (R.M.B.), The University of Tulsa, Tulsa, Oklahoma 74104; Unité Mixte de Recherche 7221 (L.S., N.B.), Muséum National d'Histoire Naturelle, Centre Nationale de Recherche Scientifique, CP32 Paris, France; Neuroscience Graduate Program (J.R.K., Y.K., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109; Genome Institute of Singapore (Y.R., X.R.), 138672 Singapore; The Jackson Laboratory of Genomic Medicine (Y.R., X.R.), Farmington, Connecticut 06030; and Department of Genetics and Developmental Biology (Y.R., X.R.), University of Connecticut, Storrs, Connecticut 06269.
Robert J DenverDepartment of Molecular, Cellular and Developmental Biology (P.D.B., S.R., R.J.D.), University of Michigan, Ann Arbor, Michigan 48109; Department of Biological Science (R.M.B.), The University of Tulsa, Tulsa, Oklahoma 74104; Unité Mixte de Recherche 7221 (L.S., N.B.), Muséum National d'Histoire Naturelle, Centre Nationale de Recherche Scientifique, CP32 Paris, France; Neuroscience Graduate Program (J.R.K., Y.K., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109; Genome Institute of Singapore (Y.R., X.R.), 138672 Singapore; The Jackson Laboratory of Genomic Medicine (Y.R., X.R.), Farmington, Connecticut 06030; and Department of Genetics and Developmental Biology (Y.R., X.R.), University of Connecticut, Storrs, Connecticut 06269.
University of Michigan–Ann Arbor · USGenome Institute of Singapore · SGJackson Laboratory · USUniversity of Tulsa · US

Funding

PUBLIC HEALTH DEMONSTRATIONP60DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MYERS, MARTIN G · 1985 to 2012
$26.5M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
Career Training in Reproductive BiologyT32HD079342 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Suzanne M MOENTER · 2014 to 2026
$2.3M
Characterization of RNA-Chromatin Interactome by RNA-DNA Ligation and SequencingR01CA186714 · NCI · JACKSON LABORATORY · PI RUAN, YIJUN · 2014 to 2016
$2.2M
Hormone and Activity-Dependent Neural Gene ExpressionR01NS046690 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DENVER, ROBERT J · 2004 to 2007
$815k
NCI NIH HHS R01 CA186714NICHD NIH HHS T32 HD079342NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P60 DK020572NIDDK NIH HHS P60 DK20572NINDS NIH HHS 1 R01 NS046690NINDS NIH HHS R01 NS046690
6 · The paper itself

Abstract

Cooperative, synergistic gene regulation by nuclear hormone receptors can increase sensitivity and amplify cellular responses to hormones. We investigated thyroid hormone (TH) and glucocorticoid (GC) synergy on the Krüppel-like factor 9 (Klf9) gene, which codes for a zinc finger transcription factor involved in development and homeostasis of diverse tissues. We identified regions of the Xenopus and mouse Klf9 genes 5-6 kb upstream of the transcription start sites that supported synergistic transactivation by TH plus GC. Within these regions, we found an orthologous sequence of approximately 180 bp that is highly conserved among tetrapods, but absent in other chordates, and possesses chromatin marks characteristic of an enhancer element. The Xenopus and mouse approximately 180-bp DNA element conferred synergistic transactivation by hormones in transient transfection assays, so we designate this the Klf9 synergy module (KSM). We identified binding sites within the mouse KSM for TH receptor, GC receptor, and nuclear factor κB. TH strongly increased recruitment of liganded GC receptor and serine 5 phosphorylated (initiating) RNA polymerase II to chromatin at the KSM, suggesting a mechanism for transcriptional synergy. The KSM is transcribed to generate long noncoding RNAs, which are also synergistically induced by combined hormone treatment, and the KSM interacts with the Klf9 promoter and a far upstream region through chromosomal looping. Our findings support that the KSM plays a central role in hormone regulation of vertebrate Klf9 genes, it evolved in the tetrapod lineage, and has been maintained by strong stabilizing selection.

Indexed as

Conserved SequenceGene Expression RegulationAcetylationAnimalsBase PairingBase SequenceBrainChromatinCortisoneEnhancer Elements, GeneticEvolution, MolecularGene Knockdown TechniquesGenetic LociHistonesKruppel-Like Transcription FactorsMice, Inbred C57BLChromatinCortisoneHistonesKruppel-Like Transcription FactorsReceptors, Cytoplasmic and NuclearReceptors, GlucocorticoidRNA, Long NoncodingRNA, MessengerRNA Polymerase IITriiodothyronine

Identifiers

PMID25866873
PMCPMC4447637
OpenAlexW2154045106

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.