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PMID: 7838715 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR gamma and RXR alpha.

Nucleic acids research ·Vol. 22 ·No. 25 ·1994-12-25 ·Pages 5628-34

Tontonoz P, Graves RA, Budavari AI, Erdjument-Bromage H, Lui M, Hu E, Tempst P, Spiegelman BM

Abstract

Previously, we identified a novel transcription factor, ARF6, as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. In order to identify the proteins which comprise the adipocyte ARF6 complex, we have purified this DNA binding activity from a cultured adipocyte cell line. We have developed a system for growth and differentiation of HIB-1B brown adipocytes in suspension culture that facilitates the production of large quantities of adipocyte nuclear extract. ARF6 was purified from HIB-1B nuclear extract by a combination of conventional and sequence-specific DNA affinity chromotography. Chemical sequencing and mass spectral analysis of tryptic peptides derived from the purified polypeptides identifies the ARF6 complex as a heterodimer of the retinoid X receptor alpha (RXR alpha) and the murine peroxisome proliferator activated receptor gamma (PPAR gamma). Of the known PPAR gamma isoforms, PPAR gamma is the predominant form expressed in adipose tissue. These results suggest that PPAR gamma 2 serves a unique function among PPAR family members as an important regulator of adipocyte-specific gene expression.

MeSH Terms
Adipocytes/physiology Adipose Tissue, Brown/chemistry Amino Acid Sequence Animals Base Sequence Cell Line DNA-Binding Proteins/chemistry Enhancer Elements, Genetic Liver/metabolism Mass Spectrometry Mice Molecular Sequence Data Oligodeoxyribonucleotides/metabolism Peptide Fragments/chemistry Receptors, Cytoplasmic and Nuclear/chemistry Receptors, Retinoic Acid/chemistry Retinoid X Receptors Transcription Factors/chemistry
Chemicals
DNA-Binding Proteins Oligodeoxyribonucleotides Peptide Fragments Receptors, Cytoplasmic and Nuclear Receptors, Retinoic Acid Retinoid X Receptors Transcription Factors
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Tontonoz P
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Graves R A
Budavari A I
Erdjument-Bromage H
Lui M
Hu E
Tempst P
Spiegelman B M
References (38)
38 references, click to expand
  1. Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid.
    Nature. 1992 Aug 13;358(6387):587-91 PMID: 1323763
  2. Preadipocytes possess cellular retinoid binding proteins and their differentiation is inhibited by retinoids.
    Biochem Biophys Res Commun. 1980 Aug 29;95(4):1839-45 PMID: 6998485
  3. Adipocyte conversion of cultured 3T3-L1 preadipocytes by bezafibrate.
    Life Sci. 1987 Mar 9;40(10):935-41 PMID: 2434818
  4. A direct role for C/EBP and the AP-I-binding site in gene expression linked to adipocyte differentiation.
    Mol Cell Biol. 1989 Dec;9(12):5331-9 PMID: 2511432
  5. Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes.
    Genes Dev. 1989 Sep;3(9):1323-35 PMID: 2606350
  6. Nuclear receptor that identifies a novel retinoic acid response pathway.
    Nature. 1990 May 17;345(6272):224-9 PMID: 2159111
  7. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators.
    Nature. 1990 Oct 18;347(6294):645-50 PMID: 2129546
  8. Internal sequence analysis of proteins separated on polyacrylamide gels at the submicrogram level: improved methods, applications and gene cloning strategies.
    Electrophoresis. 1990 Jul;11(7):537-53 PMID: 2226409
  9. A fat-specific enhancer is the primary determinant of gene expression for adipocyte P2 in vivo.
    Proc Natl Acad Sci U S A. 1990 Dec;87(24):9590-4 PMID: 2263614
  10. Metabolic effects of developmental, tissue-, and cell-specific expression of a chimeric phosphoenolpyruvate carboxykinase (GTP)/bovine growth hormone gene in transgenic mice.
    J Biol Chem. 1990 Dec 25;265(36):22371-9 PMID: 1702419
  11. Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily.
    Genes Dev. 1990 Dec;4(12B):2353-65 PMID: 2279702
  12. Identification of a potent adipocyte-specific enhancer: involvement of an NF-1-like factor.
    Genes Dev. 1991 Mar;5(3):428-37 PMID: 2001842
  13. A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR.
    Cell. 1991 Aug 9;66(3):555-61 PMID: 1651173
  14. Purification of sequence-specific binding proteins by DNA affinity chromatography.
    Methods Enzymol. 1991;208:10-23 PMID: 1779831
  15. Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling.
    Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1448-52 PMID: 1311101
  16. Tissue-specific, developmental, hormonal, and dietary regulation of rat phosphoenolpyruvate carboxykinase-human growth hormone fusion genes in transgenic mice.
    Mol Cell Biol. 1992 Mar;12(3):1007-20 PMID: 1545785
  17. Analysis of a tissue-specific enhancer: ARF6 regulates adipogenic gene expression.
    Mol Cell Biol. 1992 Mar;12(3):1202-8 PMID: 1545801
  18. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors.
    Cell. 1992 Mar 6;68(5):879-87 PMID: 1312391
  19. Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor.
    Proc Natl Acad Sci U S A. 1992 May 15;89(10):4653-7 PMID: 1316614
  20. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors.
    Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7355-9 PMID: 8041794
  21. Microbore reversed-phase high-performance liquid chromatographic purification of peptides for combined chemical sequencing-laser-desorption mass spectrometric analysis.
    J Chromatogr A. 1994 Jul 29;676(1):121-37 PMID: 7921170
  22. mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer.
    Genes Dev. 1994 May 15;8(10):1224-34 PMID: 7926726
  23. Hibernoma formation in transgenic mice and isolation of a brown adipocyte cell line expressing the uncoupling protein gene.
    Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7561-5 PMID: 1323843
  24. Cellular and molecular aspects of adipose tissue development.
    Annu Rev Nutr. 1992;12:207-33 PMID: 1503804
  25. Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors.
    Nature. 1992 Aug 27;358(6389):771-4 PMID: 1324435
  26. Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids.
    Mol Endocrinol. 1992 Oct;6(10):1634-41 PMID: 1333051
  27. Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers.
    Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2160-4 PMID: 8384714
  28. Regulation of adipocyte gene expression in differentiation and syndromes of obesity/diabetes.
    J Biol Chem. 1993 Apr 5;268(10):6823-6 PMID: 8463205
  29. Increase of adipose differentiation by hypolipidemic fibrate drugs in Ob 17 preadipocytes: requirement for thyroid hormones.
    Biochim Biophys Acta. 1993 May 8;1177(1):8-14 PMID: 8485171
  30. Targeted expression of a toxin gene to adipose tissue: transgenic mice resistant to obesity.
    Genes Dev. 1993 Jul;7(7B):1318-24 PMID: 8330737
  31. Adipose cell hyperplasia and enhanced glucose disposal in transgenic mice overexpressing GLUT4 selectively in adipose tissue.
    J Biol Chem. 1993 Oct 25;268(30):22243-6 PMID: 8226728
  32. Identification of two mPPAR related receptors and evidence for the existence of five subfamily members.
    Biochem Biophys Res Commun. 1993 Oct 29;196(2):671-7 PMID: 8240342
  33. Cloning of a new member of the peroxisome proliferator-activated receptor gene family from mouse liver.
    J Biol Chem. 1993 Dec 25;268(36):26817-20 PMID: 8262913
  34. Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte phenotype and survival.
    Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1786-90 PMID: 8127882
  35. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  36. Contacts between Escherichia coli RNA polymerase and an early promoter of phage T7.
    Proc Natl Acad Sci U S A. 1980 Jan;77(1):122-6 PMID: 6987648
  37. Control of specific protein biosynthesis during the adipose conversion of 3T3 cells.
    J Biol Chem. 1980 Sep 25;255(18):8811-18 PMID: 6773950
  38. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei.
    Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 PMID: 6828386
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/22.25.5628
Published
1994-12-25
Pages
5628-34
Language
English
Region
England
NLM ID
0411011
PMCID
PMC310126
Subset
IM
Grants
NIGMS NIH HHS · T32 GM007753 · United States
NCI NIH HHS · 5 P30 CA08748-9 · United States
NIDDK NIH HHS · DK31405 · United States
NIGMS NIH HHS · T32 GM07753-14 · United States
External Links
PubMed source DOI: 10.1093/nar/22.25.5628 PMC Full Text View journal details
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