Signaling by Nuclear Receptors
Open accessAbstract
Nuclear receptors are a family of ligand-regulated transcription factors that are activated by steroid hormones, such as estrogen and progesterone, and various other lipid-soluble signals, including retinoic acid, oxysterols, and thyroid hormone (Mangelsdorf et al. 1995).Unlike most intercellular messengers, the ligands can cross the plasma membrane and directly interact with nuclear receptors inside the cell (Fig. 1), rather than having to act via cell surface Cytoplasm Nucleus Coactivators Coactivators Cytosolic effects Type I/III e.g., estrogen Type II (extracellular ligand) e.g., thyroid hormone Corepressors TRE/LXRE ERE ER HSP HSP ER
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The study examined expression patterns of several transcription factor families (Fox, Klf, Lhx, Nkx, Nr, Pax, Pou, Prdm, Sox, Tbx), all of which have been shown to have important roles in spatial patterning, cell-type specification and differentiation during development.
“We examined the expression patterns of several transcription factor families (Extended Data Fig. 13), including forkhead box (Fox), Krüppel-like factor (Klf), LIM homeobox (Lhx), NKX-homeodomain (Nkx), nuclear receptor (Nr), Paired box (Pax), POU domain (Pou), positive regulatory domain (Prdm), SRY-related HMG-box (Sox), and T-box (Tbx), all of which have been shown to have important roles in”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [105]
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Experimental — accuracy not yet measuredeRegulons depend on nutritional status (AGMAT, MLXIPL), hormone levels (NR1I2, NR1I3, RXRA), and circadian rhythm (CLOCK).
“This enabled us to identify eRegulons that depend on nutritional status, such as AGMAT30 and MLXIPL31; on hormone levels, such as NR1I2, NR1I3 and RXRA32; and on circadian rhythm, such as CLOCK33.”
From Single-cell spatial multi-omics and deep learning dissect enhancer-driven gene regulatory networks in liver zonation (2024) · cites this paper as [32]
The Abstract (page not provided) describes hormone-regulated nuclear-receptor transcription, and Table 1 identifies RXR as a receptor with a ligand. But the copy does not identify NR1I2 or NR1I3 or establish that eRegulons associated with these three genes depend on hormone levels. The nutritional-status and circadian-rhythm examples have separate citations and are not assessed here. (LLM, conf=0.83)
Experimental — accuracy not yet measuredRegulons that depend on nutritional status include Agmat and Mlxipl; on hormone levels include Nr1i2, Nr1i3 and Rxra; and on circadian rhythm include Clock.
“This allowed us to identify regulons that depend on nutritional status, such as Agmat52 and Mlxipl53; on hormone levels, such as Nr1i2, Nr1i3 and Rxra54; and on circadian rhythm, such as Clock55.”
From Enhancer grammar of liver cell types and hepatocyte zonation states (2022) · cites this paper as [54]
Only the hormone-level examples are attributed to this source by citation 54. The paper’s nuclear-receptor discussion (section labeled Abstract; page unavailable) describes hormone-responsive transcription and identifies RXR as a receptor that partners with the thyroid hormone receptor. It does not identify Nr1i2 or Nr1i3 or establish that regulons for all three depend on hormone levels. (LLM, conf=0.82)
Experimental — accuracy not yet measuredActivation of type-1 nuclear receptors by their natural ligand occurs prior to dimerization in the cytoplasm via removal of a stabilizing heat shock protein, aiming straight for gene transcription in the cell nucleus.
“Activation of type-1 NRs by their natural ligand occurs prior to dimerization in the cytoplasm via the removal of a stabilizing heat shock protein (HSP) aiming straight for gene transcription in the cell nucleus.[41]”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [41]
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Cites
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A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
Yao, Z., van Velthoven, C. T. J., Kunst, M., Zhang, M., McMillen, D., Lee, C., Jung, W., Goldy, J., Abdelhak, A., Aitken, M., et al. (2023) · Nature · doi:10.1038/s41586-023-06812-z · Cited by 1,194 · see citing works
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“This enabled us to identify eRegulons that depend on nutritional status, such as AGMAT 30 and MLXIPL 31 ; on hormone levels, such as NR1I2, NR1I3 and RXRA 32 ; and on circadian rhythm, such as CLOCK 33 .”
Nuclear receptors in liver fibrosis
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Enhancer grammar of liver cell types and hepatocyte zonation states
González-Blas, C. B., Matetovici, I., Hillen, H., Taskiran, I. I., Vandepoel, R., Christiaens, V., Sansores-García, L., Verboven, E., Hulselmans, G., Poovathingal, S., et al. (2022) · doi:10.1101/2022.12.08.519575 · Cited by 5 · see citing works
- Authors
- Sever, R., & Glass, C. K.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- University of California San Diego (US)
- Venue
- Cold Spring Harbor Perspectives in Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2013-03-01
- Volume
- 5
- Issue
- 3
- Pages
- a016709-a016709
- ISSN
- 1943-0264 (ISSN-L)
- PMC
- PMC3578364
- OpenAlex
- W2135782451
- Cited by
- 374
- References
- 22
- Citations by year
- 2026: 15 · 2025: 28 · 2024: 69 · 2023: 42 · 2022: 47 · 2021: 45 · 2020: 41 · 2019: 31 · 2018: 22 · 2017: 12 · 2016: 13 · 2015: 6 · 2014: 2 · 2013: 1
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- nuclear receptors, steroid hormones, estrogen, progesterone, retinoic acid, oxysterols, thyroid hormones, transcriptional coactivator, corepressors, transcriptional activation, transrepression
- MeSH terms
- Humans, Ligands, Models, Biological, Organ Specificity, Protein Processing, Post-Translational, Signal Transduction, Receptors, Cytoplasmic and Nuclear
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