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PMID: 16923397 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network.

Cell ·Vol. 126 ·No. 4 ·2006-08-25 ·Pages 789-99

Bookout AL, Jeong Y, Downes M, Yu RT, Evans RM, Mangelsdorf DJ

Abstract

In multicellular organisms, the ability to regulate reproduction, development, and nutrient utilization coincided with the evolution of nuclear receptors (NRs), transcription factors that utilize lipophilic ligands to mediate their function. Studying the expression profile of NRs offers a simple, powerful way to obtain highly relational information about their physiologic functions as individual proteins and as a superfamily. We surveyed the expression of all 49 mouse NR mRNAs in 39 tissues, representing diverse anatomical systems. The resulting data set uncovers several NR clades whose patterns of expression indicate their ability to coordinate the transcriptional programs necessary to affect distinct physiologic pathways. Remarkably, this regulatory network divides along the following two physiologic paradigms: (1) reproduction, development, and growth and (2) nutrient uptake, metabolism, and excretion. These data reveal a hierarchical transcriptional circuitry that extends beyond individual tissues to form a meganetwork governing physiology on an organismal scale.

MeSH Terms
Animals Cluster Analysis Databases, Factual Female Gene Expression Profiling Male Mice Mice, Inbred C57BL Multigene Family Phylogeny Receptors, Cytoplasmic and Nuclear/classification,genetics,metabolism Tissue Distribution Transcription, Genetic
Chemicals
Receptors, Cytoplasmic and Nuclear
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bookout Angie L
Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, 75390, USA.
Jeong Yangsik
Downes Michael
Yu Ruth T
Evans Ronald M
Mangelsdorf David J
References (61)
61 references, click to expand
  1. nor-1 regulates hippocampal axon guidance, pyramidal cell survival, and seizure susceptibility.
    Mol Cell Biol. 2004 Oct;24(20):9070-8 PMID: 15456880
  2. Principles for modulation of the nuclear receptor superfamily.
    Nat Rev Drug Discov. 2004 Nov;3(11):950-64 PMID: 15520817
  3. Inactivation of the glucocorticoid receptor in hepatocytes leads to fasting hypoglycemia and ameliorates hyperglycemia in streptozotocin-induced diabetes mellitus.
    Mol Endocrinol. 2004 Jun;18(6):1346-53 PMID: 15031319
  4. High postnatal lethality and testis degeneration in retinoic acid receptor alpha mutant mice.
    Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7225-9 PMID: 8394014
  5. Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells.
    Cancer Cell. 2004 Aug;6(2):129-37 PMID: 15324696
  6. Temperature homeostasis in transgenic mice lacking thyroid hormone receptor-alpha gene products.
    Endocrinology. 2005 Jul;146(7):2872-84 PMID: 15845618
  7. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor.
    Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3920-5 PMID: 16473946
  8. Genes essential for early events in gonadal development.
    Ann Med. 2002;34(3):171-8 PMID: 12173687
  9. Identification of a photoreceptor cell-specific nuclear receptor.
    Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):4814-9 PMID: 10220376
  10. The vitamin D hormone and its nuclear receptor: molecular actions and disease states.
    J Endocrinol. 1997 Sep;154 Suppl:S57-73 PMID: 9379138
  11. Nuclear receptors and lipid physiology: opening the X-files.
    Science. 2001 Nov 30;294(5548):1866-70 PMID: 11729302
  12. Thyroid hormone action on liver, heart, and energy expenditure in thyroid hormone receptor beta-deficient mice.
    Endocrinology. 1998 Dec;139(12):4945-52 PMID: 9832432
  13. Nuclear receptor expression links the circadian clock to metabolism.
    Cell. 2006 Aug 25;126(4):801-10 PMID: 16923398
  14. Action of retinoids on embryonic and early postnatal testis development.
    Endocrinology. 1999 May;140(5):2343-52 PMID: 10218988
  15. The function of vitamin D receptor in vitamin D action.
    J Biochem. 2000 May;127(5):717-22 PMID: 10788778
  16. Chicken ovalbumin upstream promoter-transcription factor members repress retinoic acid-induced Cdx1 expression.
    J Biol Chem. 2005 Apr 8;280(14):13858-62 PMID: 15677473
  17. A Nuclear Receptor Atlas: 3T3-L1 adipogenesis.
    Mol Endocrinol. 2005 Oct;19(10):2437-50 PMID: 16051663
  18. Thyroid hormone receptor beta-deficient mice show complete loss of the normal cholesterol 7alpha-hydroxylase (CYP7A) response to thyroid hormone but display enhanced resistance to dietary cholesterol.
    Mol Endocrinol. 2000 Nov;14(11):1739-49 PMID: 11075809
  19. Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR.
    Genes Dev. 2004 Jan 15;18(2):157-69 PMID: 14729567
  20. Retinoid x receptor heterodimers in the metabolic syndrome.
    N Engl J Med. 2005 Aug 11;353(6):604-15 PMID: 16093469
  21. Beyond CAR and PXR.
    Curr Drug Metab. 2005 Aug;6(4):385-97 PMID: 16101576
  22. Regulation of PPARgamma coactivator 1alpha (PGC-1alpha) signaling by an estrogen-related receptor alpha (ERRalpha) ligand.
    Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8912-7 PMID: 15184675
  23. SF-1, DAX-1, and acd: molecular determinants of adrenocortical growth and steroidogenesis.
    Endocr Res. 2002 Nov;28(4):597-607 PMID: 12530669
  24. Deficits in motor coordination with aberrant cerebellar development in mice lacking testicular orphan nuclear receptor 4.
    Mol Cell Biol. 2005 Apr;25(7):2722-32 PMID: 15767677
  25. The nuclear receptor superfamily: the second decade.
    Cell. 1995 Dec 15;83(6):835-9 PMID: 8521507
  26. Functions of thyroid hormone receptors in mice.
    Thyroid. 2000 Jan;10(1):41-52 PMID: 10691312
  27. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c.
    J Clin Invest. 2004 May;113(10):1408-18 PMID: 15146238
  28. Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor alpha.
    Mol Cell Biol. 2003 Nov;23(22):7947-56 PMID: 14585956
  29. Retinoic acid receptor alpha is required for synchronization of spermatogenic cycles and its absence results in progressive breakdown of the spermatogenic process.
    Dev Dyn. 2004 Aug;230(4):754-66 PMID: 15254909
  30. Vitamin D receptor as an intestinal bile acid sensor.
    Science. 2002 May 17;296(5571):1313-6 PMID: 12016314
  31. The role of orphan nuclear receptor in thymocyte differentiation and lymphoid organ development.
    Immunol Res. 2000;22(2-3):71-82 PMID: 11339367
  32. Quantitative real-time PCR protocol for analysis of nuclear receptor signaling pathways.
    Nucl Recept Signal. 2003;1:e012 PMID: 16604184
  33. PXR, CAR and drug metabolism.
    Nat Rev Drug Discov. 2002 Apr;1(4):259-66 PMID: 12120277
  34. Molecular mechanism of chicken ovalbumin upstream promoter-transcription factor (COUP-TF) actions.
    Keio J Med. 2003 Sep;52(3):174-81 PMID: 14529150
  35. Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos.
    Genes Dev. 1994 Oct 15;8(20):2466-77 PMID: 7958910
  36. The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis.
    Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6472-7 PMID: 15087503
  37. Identification of farnesoid X receptor beta as a novel mammalian nuclear receptor sensing lanosterol.
    Mol Cell Biol. 2003 Feb;23(3):864-72 PMID: 12529392
  38. Characterization of a vitamin D receptor knockout mouse as a model of colorectal hyperproliferation and DNA damage.
    Carcinogenesis. 2001 Sep;22(9):1429-35 PMID: 11532865
  39. PPARs and the complex journey to obesity.
    Nat Med. 2004 Apr;10(4):355-61 PMID: 15057233
  40. Physiological function of the orphans GCNF and COUP-TF.
    Trends Endocrinol Metab. 2001 Aug;12(6):247-51 PMID: 11445441
  41. Liver X receptor signaling pathways in cardiovascular disease.
    Mol Endocrinol. 2003 Jun;17(6):985-93 PMID: 12690094
  42. A decade of molecular biology of retinoic acid receptors.
    FASEB J. 1996 Jul;10(9):940-54 PMID: 8801176
  43. Recent advances in the TR2 and TR4 orphan receptors of the nuclear receptor superfamily.
    J Steroid Biochem Mol Biol. 2002 Aug;81(4-5):291-308 PMID: 12361719
  44. Mineralocorticoids, salt and high blood pressure.
    Steroids. 1996 Apr;61(4):184-8 PMID: 8732997
  45. Molecular determinants of crosstalk between nuclear receptors and toll-like receptors.
    Cell. 2005 Sep 9;122(5):707-21 PMID: 16143103
  46. Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate.
    Nat Genet. 2000 Feb;24(2):127-31 PMID: 10655056
  47. Abnormal development of the locus coeruleus in Ear2(Nr2f6)-deficient mice impairs the functionality of the forebrain clock and affects nociception.
    Genes Dev. 2005 Mar 1;19(5):614-25 PMID: 15741322
  48. BAREing it all: the adoption of LXR and FXR and their roles in lipid homeostasis.
    J Lipid Res. 2002 Jan;43(1):2-12 PMID: 11792716
  49. Genetic dissection of corticosteroid receptor function in mice.
    Horm Metab Res. 2004 Jun;36(6):387-91 PMID: 15241729
  50. Expression and function of orphan nuclear receptor TLX in adult neural stem cells.
    Nature. 2004 Jan 1;427(6969):78-83 PMID: 14702088
  51. Nurr1, an orphan nuclear receptor with essential functions in developing dopamine cells.
    Cell Tissue Res. 2004 Oct;318(1):45-52 PMID: 15340833
  52. Nuclear hormone receptors in T lymphocytes.
    Cell. 2002 Apr;109 Suppl:S57-66 PMID: 11983153
  53. Expression and function of the human mineralocorticoid receptor: lessons from transgenic mouse models.
    Mol Cell Endocrinol. 2004 Mar 31;217(1-2):127-36 PMID: 15134811
  54. A Nuclear Receptor Atlas: macrophage activation.
    Mol Endocrinol. 2005 Oct;19(10):2466-77 PMID: 16051664
  55. The farnesoid X receptor modulates hepatic carbohydrate metabolism during the fasting-refeeding transition.
    J Biol Chem. 2005 Aug 19;280(33):29971-9 PMID: 15899888
  56. LXRs regulate the balance between fat storage and oxidation.
    Cell Metab. 2005 Apr;1(4):231-44 PMID: 16054068
  57. Molecular etiologies of MODY and other early-onset forms of diabetes.
    Curr Diab Rep. 2002 Apr;2(2):125-34 PMID: 12643132
  58. Orphan nuclear receptors as eLiXiRs and FiXeRs of sterol metabolism.
    J Biol Chem. 2001 Oct 12;276(41):37735-8 PMID: 11459853
  59. A deletion in a photoreceptor-specific nuclear receptor mRNA causes retinal degeneration in the rd7 mouse.
    Proc Natl Acad Sci U S A. 2000 May 9;97(10):5551-6 PMID: 10805811
  60. Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis.
    Mol Cell Biol. 2001 Feb;21(4):1393-403 PMID: 11158324
  61. Chicken ovalbumin upstream promoter-transcription factors and their regulation.
    J Steroid Biochem Mol Biol. 1996 Jan;56(1-6 Spec No):81-5 PMID: 8603050
Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/j.cell.2006.06.049
Published
2006-08-25
Pages
789-99
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC6211849
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NIDDK NIH HHS · U19 DK062434 · United States
NIDDK NIH HHS · U19DK62434 · United States
External Links
PubMed source DOI: 10.1016/j.cell.2006.06.049 PMC Full Text View journal details
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