Evidence map›Paper›PMID 27582276›Full record

ArticleCell communication and signaling : CCS2016

Epigenetic regulation of transcription factor promoter regions by low-dose genistein through mitogen-activated protein kinase and mitogen-and-stress activated kinase 1 nongenomic signaling.

Linda Yu, Kyle Ham, Xiaohua Gao, Lysandra Castro, Yitang Yan, Grace E Kissling, Charles J Tucker, Norris Flagler, Ray Dong, Trevor K Archer and 1 more

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

Article in Cell communication and signaling : CCS, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

7 citing papers in PubMed, 16 citations in OpenAlex.

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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

11 authors at 3 institutions in 1 country.

Linda YuMolecular Pathogenesis Group, National Toxicology Program (NTP) Laboratory, Division of the NTP (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), U.S. Department of Health and Human Services (HHS), Research Triangle Park, North Carolina, 27709, USA.
Kyle HamMolecular Pathogenesis Group, National Toxicology Program (NTP) Laboratory, Division of the NTP (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), U.S. Department of Health and Human Services (HHS), Research Triangle Park, North Carolina, 27709, USA.
Xiaohua GaoMolecular Pathogenesis Group, National Toxicology Program (NTP) Laboratory, Division of the NTP (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), U.S. Department of Health and Human Services (HHS), Research Triangle Park, North Carolina, 27709, USA.
Lysandra CastroMolecular Pathogenesis Group, National Toxicology Program (NTP) Laboratory, Division of the NTP (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), U.S. Department of Health and Human Services (HHS), Research Triangle Park, North Carolina, 27709, USA.
Yitang YanMolecular Pathogenesis Group, National Toxicology Program (NTP) Laboratory, Division of the NTP (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), U.S. Department of Health and Human Services (HHS), Research Triangle Park, North Carolina, 27709, USA.
Grace E KisslingBiostatistics and Computational Biology Branch, Division of Intramural Research (DIR), NIEHS, NIH, HHS, Research Triangle Park, North Carolina, 27709, USA.
Charles J TuckerSignal Transduction Laboratory, DIR, NIEHS, NIH, HHS, Research Triangle Park, North Carolina, 27709, USA.
Norris FlaglerCellular and Molecular Pathology Branch, DNTP, NIEHS, NIH, HHS, Research Triangle Park, North Carolina, 27709, USA.
Ray DongMolecular Pathogenesis Group, National Toxicology Program (NTP) Laboratory, Division of the NTP (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), U.S. Department of Health and Human Services (HHS), Research Triangle Park, North Carolina, 27709, USA.
Trevor K ArcherChromatin and Gene Expression Group, Epigenetics and Stem Cell Biology Laboratory, DIR, NIEHS, NIH, HHS, Research Triangle Park, North Carolina, 27709, USA.
Darlene DixonMolecular Pathogenesis Group, National Toxicology Program (NTP) Laboratory, Division of the NTP (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), U.S. Department of Health and Human Services (HHS), Research Triangle Park, North Carolina, 27709, USA. dixon@niehs.nih.gov.ORCID 0000-0002-7001-2985
National Institutes of Health · USNational Institute of Environmental Health Sciences · USResearch Triangle Park Foundation · US

Funding

Transcriptional Functions of Nuclear Receptors in Cancer CellsZIAES071006 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ARCHER, TREVOR KEITH · 2009 to 2025
$58.0M
Pathobiology Of Uterine Leiomyomas (fibroids)ZIAES021196 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI DIXON, DARLENE · 2009 to 2025
$31.7M
Statistical collaboration in environmental health researchZIAES103106 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KISSLING, GRACE E · 2012 to 2017
$656k
6 · The paper itself

Abstract

backgroundThe phytoestrogen, genistein at low doses nongenomically activates mitogen-activated protein kinase p44/42 (MAPKp44/42) via estrogen receptor alpha (ERα) leading to proliferation of human uterine leiomyoma cells. In this study, we evaluated if MAPKp44/42 could activate downstream effectors such as mitogen- and stress-activated protein kinase 1 (MSK1), which could then epigenetically modify histone H3 by phosphorylation following a low dose (1 μg/ml) of genistein.

resultsUsing hormone-responsive immortalized human uterine leiomyoma (ht-UtLM) cells, we found that genistein activated MAPKp44/42 and MSK1, and also increased phosphorylation of histone H3 at serine10 (H3S10ph) in ht-UtLM cells. Colocalization of phosphorylated MSK1 and H3S10ph was evident by confocal microscopy in ht-UtLM cells (r = 0.8533). Phosphorylation of both MSK1and H3S10ph was abrogated by PD98059 (PD), a MEK1 kinase inhibitor, thereby supporting genistein's activation of MSK1 and Histone H3 was downstream of MAPKp44/42. In proliferative (estrogenic) phase human uterine fibroid tissues, phosphorylated MSK1 and H3S10ph showed increased immunoexpression compared to normal myometrial tissues, similar to results observed in in vitro studies following low-dose genistein administration. Real-time RT-PCR arrays showed induction of growth-related transcription factor genes, EGR1, Elk1, ID1, and MYB (cMyb) with confirmation by western blot, downstream of MAPK in response to low-dose genistein in ht-UtLM cells. Additionally, genistein induced associations of promoter regions of the above transcription factors with H3S10ph as evidenced by Chromatin Immunoprecipitation (ChIP) assays, which were inhibited by PD. Therefore, genistein epigenetically modified histone H3 by phosphorylation of serine 10, which was regulated by MSK1 and MAPK activation.

conclusionHistone H3 phosphorylation possibly represents a mechanism whereby increased transcriptional activation occurs following low-dose genistein exposure.

Indexed as

Epigenesis, GeneticPromoter Regions, GeneticAntineoplastic AgentsCell Line, TumorGenisteinHistonesHumansMAP Kinase Signaling SystemMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PhosphorylationProtein Processing, Post-TranslationalRibosomal Protein S6 Kinases, 90-kDaTranscriptional ActivationTranscription FactorsAntineoplastic AgentsGenisteinHistonesMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3mitogen and stress-activated protein kinase 1Ribosomal Protein S6 Kinases, 90-kDaTranscription FactorsEpigeneticHistone H3LeiomyomaMAPKp44/42MSK1

Identifiers

PMID27582276
PMCPMC5007815
OpenAlexW2513967744

What OpenQuestion holds

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LicenceCC BY
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.