Cited by 333Developmental Biology and Gene RegulationToxic Organic Pollutants ImpactCancer, Hypoxia, and Metabolism

Expression of ARNT, ARNT2, HIF1α, HIF2α and Ah receptor mRNAs in the developing mouse

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Jain, Sanjay, Maltepe, Emin, Lu, Min M, Simon, Celeste, Bradfield, Christopher A·1998·Mechanisms of Development

Abstract

The basic helix-loop-helix-PAS (bHLH-PAS) protein ARNT is a dimeric partner of the Ah receptor (AHR) and hypoxia inducible factor 1 alpha(HIF1 alpha). These dimers mediate biological responses to xenobiotic exposure and low oxygen tension. The recent cloning of ARNT and HIF1(homologues (ARNT2 and HIF2 alpha) indicates that at least six distinct bHLH-PAS heterodimeric combinations can occur in response to a number of environmental stimuli. In an effort to understand the biological relevance of this combinatorial complexity, we characterized their relative expression at a number of developmental time points by parallel in situ hybridization of adjacent tissue sections. Our results reveal that in general there is limited redundancy in the expression of these six transcription factors and that each of these bHLH-PAS members displays a unique pattern of developmental expression emerging as early as embryonic day 9.5.

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Crossref · 10.1016/s0925-4773(98)00038-0

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  • AHR's role is highly context-dependent, with receptor number, cell type, and developmental window differentially influencing outcomes of receptor activation.

    “This study supported previous studies from other laboratories regarding the highly context-dependent role of AHR (S. Jain et al., 1998; Willey et al., 1998). That is, factors such as receptor number, cell type, and developmental window can differentially influence the outcome of receptor activation.”

    From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as S. Jain et al., 1998

    The Abstract and the E13.5d in situ hybridization section report that AHR and related factors have distinct expression patterns across developmental stages and tissues. This supports the cell-type and developmental-window aspects of context dependence, but the paper measures mRNA expression, not receptor number or differences in the outcomes of AHR activation. (LLM, conf=0.85)

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Research works printed but not linked: 3

  1. Ausubel, F.M., Brent, R., Kingston, R.E., Moore, D.D., Seidman, J.G., Smith, J.A., Struhl, K., 1990. Current Protocols in Molecular Biology, Volume 1, Greene Publishing Associates and Wiley-Interscience, New York.
  2. Burbach, K.M., Poland, A., Bradfield, C.A., 1992. Cloning of the Ah receptor cDNA reveals a distinctive ligand-activated transcription factor. Proc. Natl. Acad. Sci. USA 89, 8185-8189.
  3. Wang, G.L., Jiang, B.H., Rue, E.A., Semenza, G.L., 1995. Hypoxia-indu- cible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O 2 tension. Proc. Natl. Acad. Sci. USA 92, 5510-5514.

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Authors
Jain, S., Maltepe, E., Lu, M. M., Simon, C., & Bradfield, C. A.
Affiliations
  • Northwestern University (US)
  • University of Chicago (US)
  • University of Wisconsin–Madison (US)
Corresponding author
Bradfield, Christopher A
Venue
Mechanisms of Development
Publisher
Elsevier BV
Published
1998-04
Volume
73
Issue
1
Pages
117-123
ISSN
0925-4773 (ISSN-L)
OpenAlex
W2024564719
Cited by
333
References
2
Citations by year
2026: 2 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 11 · 2021: 9 · 2020: 8 · 2019: 3 · 2018: 11 · 2017: 10 · 2016: 7 · 2015: 15 · 2014: 9 · 2013: 10 · 2012: 3
FWCI
5.13
Type
journal article
Language
en
Open access
Locations
  • Mechanisms of Development (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health (5p30ca007175-36)
  • National Cancer Institute (P30 CA 07175)
  • National Institute of Environmental Health Sciences (ES06883, R01ES006883)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
ARNT, ARNT2, HIF-1α, HIF-2α, Ah receptor, bHLH-PAS transcription factors, heterodimeric transcription factors, hypoxia response, xenobiotic response
MeSH terms
Animals, Animals, Newborn, DNA-Binding Proteins, Embryo, Mammalian, Genes, Overlapping, Mice, Inbred C57BL, Nuclear Proteins, RNA, Messenger, Transcription Factors, In Situ Hybridization, Receptors, Aryl Hydrocarbon, Mice, Aryl Hydrocarbon Receptor Nuclear Translocator, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit

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