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PMID: 12727880 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Stimulation of preadipocyte differentiation by steroid through targeting of an HDAC1 complex.

The EMBO journal ·Vol. 22 ·No. 9 ·2003-05-01 ·Pages 2135-45

Wiper-Bergeron N, Wu D, Pope L, Schild-Poulter C, Haché RJ

Abstract

Glucocorticoids potentiate the early steps of preadipocyte differentiation and promote obesity in Cushing's syndrome and during prolonged steroid therapy. We show that glucocorticoids stimulate 3T3 L1 preadipocyte differentiation through a non-transcriptional mechanism mediated through the ligand-binding domain of the glucocorticoid receptor. This enhanced the onset of CCAAT/enhancer binding protein (C/EBPalpha) expression by potentiating its initial transcriptional activation by C/EBPbeta. In the absence of steroid, C/EBPbeta associated with a transcriptional corepressor complex containing mSin3A and histone deacetylase 1 (HDAC1), but lacking HDAC2 and RbAp46/48. HDAC1/mSin3A were recruited to the C/EBPalpha promoter with C/EBPbeta and promoted the deacetylation of histone H4. Steroid induced the specific depletion of this corepressor by targeting the HDAC1 within the complex for degradation through the 26S proteasome. Treatment with histone deacetylase inhibitors replaced the effects of steroid treatment on preadipocyte differentiation and C/EBPalpha expression, while overexpression of HDAC1 abrogated the stimulatory effects of steroid. Recapitulation of the glucocorticoid effect by progestin treatment in the presence of the progesterone receptor ligand-binding domain suggests a conserved mechanism relevant to many aspects of steroid-mediated differentiation.

MeSH Terms
3T3 Cells Adipocytes/cytology,drug effects Animals CCAAT-Enhancer-Binding Protein-alpha/genetics COS Cells Cell Differentiation/drug effects Glucocorticoids/pharmacology HeLa Cells Histone Deacetylase 1 Histone Deacetylases/metabolism Humans Mice Repressor Proteins/metabolism Sin3 Histone Deacetylase and Corepressor Complex
Chemicals
CCAAT-Enhancer-Binding Protein-alpha Glucocorticoids Repressor Proteins SIN3A transcription factor HDAC1 protein, human Histone Deacetylase 1 Histone Deacetylases Sin3 Histone Deacetylase and Corepressor Complex
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Wiper-Bergeron Nadine
The Ottawa Health Research Institute, University of Ottawa, 725 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9.
Wu Dongmei
Pope Louise
Schild-Poulter Caroline
Haché Robert J G
References (58)
58 references, click to expand
  1. Ligand-dependent interaction of the glucocorticoid receptor with p53 enhances their degradation by Hdm2.
    Genes Dev. 2001 Sep 15;15(18):2367-80 PMID: 11562347
  2. Activation and centromeric localization of CCAAT/enhancer-binding proteins during the mitotic clonal expansion of adipocyte differentiation.
    Genes Dev. 1999 Sep 1;13(17):2231-41 PMID: 10485846
  3. Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300-binding protein.
    Genes Dev. 2001 Oct 1;15(19):2598-612 PMID: 11581164
  4. Class I histone deacetylases sequentially interact with MyoD and pRb during skeletal myogenesis.
    Mol Cell. 2001 Oct;8(4):885-97 PMID: 11684023
  5. Proteasome-mediated glucocorticoid receptor degradation restricts transcriptional signaling by glucocorticoids.
    J Biol Chem. 2001 Nov 16;276(46):42714-21 PMID: 11555652
  6. Bodyweight gain and anticonvulsants: a comparative review.
    Drug Saf. 2001;24(13):969-78 PMID: 11735653
  7. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells.
    EMBO J. 2001 Dec 17;20(24):6969-78 PMID: 11742974
  8. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway.
    Genes Dev. 2002 Jan 1;16(1):22-6 PMID: 11782441
  9. Decrements in nuclear glucocorticoid receptor (GR) protein levels and DNA binding in aged rat hippocampus.
    Endocrinology. 2002 Apr;143(4):1362-70 PMID: 11897693
  10. Cooperation between complexes that regulate chromatin structure and transcription.
    Cell. 2002 Feb 22;108(4):475-87 PMID: 11909519
  11. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro.
    Mol Cell. 1999 Oct;4(4):611-7 PMID: 10549292
  12. Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26S proteasome.
    Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1032-7 PMID: 10655479
  13. C/EBPbeta (CCAAT/enhancer binding protein) controls cell fate determination during mammary gland development.
    Mol Endocrinol. 2000 Mar;14(3):359-68 PMID: 10707954
  14. 1999 Curt P. Richter award. Glucocorticoids and the regulation of memory consolidation.
    Psychoneuroendocrinology. 2000 Apr;25(3):213-38 PMID: 10737694
  15. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1beta-induced histone H4 acetylation on lysines 8 and 12.
    Mol Cell Biol. 2000 Sep;20(18):6891-903 PMID: 10958685
  16. Modulation of the murine peroxisome proliferator-activated receptor gamma 2 promoter activity by CCAAT/enhancer-binding proteins.
    J Biol Chem. 2000 Sep 8;275(36):27815-22 PMID: 10862621
  17. Corticosteroids: sculptors of the hippocampal formation.
    Rev Neurosci. 2002;13(1):59-84 PMID: 12013026
  18. Role of adrenal stress hormones in forming lasting memories in the brain.
    Curr Opin Neurobiol. 2002 Apr;12(2):205-10 PMID: 12015238
  19. Development of hormone receptors and hormonal responsiveness in vitro. Insulin receptors and insulin sensitivity in the preadipocyte and adipocyte forms of 3T3-L1 cells.
    J Biol Chem. 1978 Oct 25;253(20):7570-8 PMID: 81205
  20. Participation of one isozyme of cytosolic glycerophosphate dehydrogenase in the adipose conversion of 3T3 cells.
    J Biol Chem. 1979 Jan 25;254(2):273-5 PMID: 762059
  21. Effect of adrenalectomy and glucocorticoid replacement on development of obesity.
    Am J Physiol. 1986 Apr;250(4 Pt 2):R595-607 PMID: 3515971
  22. Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone.
    Cell. 1990 Sep 21;62(6):1189-204 PMID: 2169351
  23. Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction.
    Cell. 1990 Sep 21;62(6):1205-15 PMID: 2169352
  24. Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor.
    Cell. 1990 Sep 21;62(6):1217-26 PMID: 2169353
  25. CCAAT/enhancer binding protein gene promoter: binding of nuclear factors during differentiation of 3T3-L1 preadipocytes.
    Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2593-7 PMID: 2006196
  26. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells.
    Genes Dev. 1991 Sep;5(9):1538-52 PMID: 1840554
  27. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription.
    Genes Dev. 1992 Mar;6(3):439-53 PMID: 1547942
  28. A nuclear factor for interleukin-6 expression (NF-IL6) and the glucocorticoid receptor synergistically activate transcription of the rat alpha 1-acid glycoprotein gene via direct protein-protein interaction.
    Mol Cell Biol. 1993 Mar;13(3):1854-62 PMID: 8441418
  29. High level activity of the mouse CCAAT/enhancer binding protein (C/EBP alpha) gene promoter involves autoregulation and several ubiquitous transcription factors.
    Nucleic Acids Res. 1993 Apr 25;21(8):1735-42 PMID: 8493090
  30. Valproic acid. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy.
    Drugs. 1994 Feb;47(2):332-72 PMID: 7512905
  31. Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells.
    Genes Dev. 1994 Jul 15;8(14):1654-63 PMID: 7958846
  32. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor.
    Cell. 1994 Dec 30;79(7):1147-56 PMID: 8001151
  33. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins.
    Genes Dev. 1995 Jan 15;9(2):168-81 PMID: 7531665
  34. Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha.
    Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9856-60 PMID: 7568232
  35. Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis.
    Genes Dev. 1995 Oct 1;9(19):2350-63 PMID: 7557387
  36. Inhibition of adipogenesis by the stress-induced protein CHOP (Gadd153).
    EMBO J. 1995 Oct 2;14(19):4654-61 PMID: 7588595
  37. The nuclear receptor superfamily: the second decade.
    Cell. 1995 Dec 15;83(6):835-9 PMID: 8521507
  38. Hypercortisolism and obesity.
    Ann N Y Acad Sci. 1995 Dec 29;771:665-76 PMID: 8597440
  39. Bodyweight change as an adverse effect of drug treatment. Mechanisms and management.
    Drug Saf. 1996 May;14(5):329-42 PMID: 8800628
  40. Retinoic acid blocks adipogenesis by inhibiting C/EBPbeta-mediated transcription.
    Mol Cell Biol. 1997 Mar;17(3):1552-61 PMID: 9032283
  41. I kappaB alpha-independent downregulation of NF-kappaB activity by glucocorticoid receptor.
    EMBO J. 1997 Aug 1;16(15):4698-707 PMID: 9303314
  42. Interaction and functional collaboration of p300 and C/EBPbeta.
    Mol Cell Biol. 1997 Nov;17(11):6609-17 PMID: 9343424
  43. Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene.
    EMBO J. 1997 Dec 15;16(24):7432-43 PMID: 9405372
  44. Dexamethasone enhances macrophage colony stimulating factor- and granulocyte macrophage colony stimulating factor-stimulated proliferation of bone marrow-derived macrophages.
    Int Immunol. 1998 May;10(5):593-9 PMID: 9645607
  45. Understanding adipocyte differentiation.
    Physiol Rev. 1998 Jul;78(3):783-809 PMID: 9674695
  46. Distinct C/EBP functions are required for eosinophil lineage commitment and maturation.
    Genes Dev. 1998 Aug 1;12(15):2413-23 PMID: 9694805
  47. AF-2-dependent potentiation of CCAAT enhancer binding protein beta-mediated transcriptional activation by glucocorticoid receptor.
    Mol Endocrinol. 1998 Nov;12(11):1749-63 PMID: 9817600
  48. Stress: metaplastic effects in the hippocampus.
    Trends Neurosci. 1998 Dec;21(12):505-9 PMID: 9881846
  49. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity.
    Mol Cell. 1999 Feb;3(2):151-8 PMID: 10078198
  50. Role of C/EBP homologous protein (CHOP-10) in the programmed activation of CCAAT/enhancer-binding protein-beta during adipogenesis.
    Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12446-50 PMID: 11050169
  51. Sequential repression and activation of the CCAAT enhancer-binding protein-alpha (C/EBPalpha ) gene during adipogenesis.
    Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12519-23 PMID: 11050170
  52. Molecular genetic analysis of glucocorticoid signaling using the Cre/loxP system.
    Biol Chem. 2000 Sep-Oct;381(9-10):961-4 PMID: 11076028
  53. Molecular genetic dissection of glucocorticoid receptor function in vivo.
    Z Rheumatol. 2000;59 Suppl 2:II/1-5 PMID: 11155788
  54. CoREST is an integral component of the CoREST- human histone deacetylase complex.
    Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1454-8 PMID: 11171972
  55. Central but not peripheral glucocorticoid infusion in adrenalectomized male rats increases basal and substrate-induced insulinemia through a parasympathetic pathway.
    Obes Res. 2001 Apr;9(4):274-81 PMID: 11331432
  56. The consolidation of new but not reactivated memory requires hippocampal C/EBPbeta.
    Nat Neurosci. 2001 Aug;4(8):813-8 PMID: 11477427
  57. Distinct transcriptional profiles of adipogenesis in vivo and in vitro.
    J Biol Chem. 2001 Sep 7;276(36):34167-74 PMID: 11445576
  58. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen.
    J Biol Chem. 2001 Sep 28;276(39):36734-41 PMID: 11473107
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg218
Published
2003-05-01
Pages
2135-45
Language
English
Region
England
NLM ID
8208664
PMCID
PMC156090
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdg218 PMC Full Text View journal details
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