Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1996 Apr;16(4):1824–1831. doi: 10.1128/mcb.16.4.1824

TFIIB-directed transcriptional activation by the orphan nuclear receptor hepatocyte nuclear factor 4.

S Malik 1, S K Karathanasis 1
PMCID: PMC231169  PMID: 8657158

Abstract

The orphan nuclear receptor hepatocyte nuclear factor 4 (HNF-4) is required for development and maintenance of the liver phenotype. HNF-4 activates several hepatocyte-specific genes, including the gene encoding apolipoprotein AI (apoAI), the major protein component of plasma high-density lipoprotein. The apoAI gene is activated by HNF-4 through a nuclear receptor binding element (site A) located in its liver-specific enhancer. To decipher the mechanism whereby HNF-4 enhances apoAI gene transcription, we have reconstituted its activity in a cell-free system. Functional HNF-4 was purified to homogeneity from a bacterial expression system. In in vitro transcription assays employing nuclear extract from HeLa cells, which do not contain HNF-4, recombinant HNF-4 stimulated transcription from basal promoters linked to site A. Activation by HNF-4 did not exhibit a ligand requirement, but phosphorylation of HNF-4 in the in vitro transcription system was observed. The activation function of HNF-4 was localized to a domain displaying strong homology to the conserved AF-2 region of nuclear receptors. Dissection of the transcription cycle revealed that HNF-4 activated transcription by facilitating assembly of a preinitiation complex intermediate consisting of TBP, the TATA box-binding protein component of TFIID and TFIID, via direct physical interactions with TFIIB. However, recruitment of TFIIB by HNF-4 was not sufficient for activation, since HNF-4 deletion derivatives lacking AF-2 bound TFIIB. On the basis of these results, HNF-4 appears to activate transcription at two distinct levels. The first step involves AF-2-independent recruitment of TFIIB to the promoter complex; the second step is AF-2 dependent and entails entry of preinitiation complex components acting downstream of TFIIB.

Full Text

The Full Text of this article is available as a PDF (471.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnold S. F., Notides A. C. An antiestrogen: a phosphotyrosyl peptide that blocks dimerization of the human estrogen receptor. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7475–7479. doi: 10.1073/pnas.92.16.7475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bagchi M. K., Tsai S. Y., Tsai M. J., O'Malley B. W. Ligand and DNA-dependent phosphorylation of human progesterone receptor in vitro. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2664–2668. doi: 10.1073/pnas.89.7.2664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baniahmad A., Ha I., Reinberg D., Tsai S., Tsai M. J., O'Malley B. W. Interaction of human thyroid hormone receptor beta with transcription factor TFIIB may mediate target gene derepression and activation by thyroid hormone. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8832–8836. doi: 10.1073/pnas.90.19.8832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barettino D., Vivanco Ruiz M. M., Stunnenberg H. G. Characterization of the ligand-dependent transactivation domain of thyroid hormone receptor. EMBO J. 1994 Jul 1;13(13):3039–3049. doi: 10.1002/j.1460-2075.1994.tb06603.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bhat M. K., Ashizawa K., Cheng S. Y. Phosphorylation enhances the target gene sequence-dependent dimerization of thyroid hormone receptor with retinoid X receptor. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7927–7931. doi: 10.1073/pnas.91.17.7927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bulla G. A., Fournier R. E. Genetic analysis of a transcriptional activation pathway by using hepatoma cell variants. Mol Cell Biol. 1994 Nov;14(11):7086–7094. doi: 10.1128/mcb.14.11.7086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Buratowski S., Hahn S., Guarente L., Sharp P. A. Five intermediate complexes in transcription initiation by RNA polymerase II. Cell. 1989 Feb 24;56(4):549–561. doi: 10.1016/0092-8674(89)90578-3. [DOI] [PubMed] [Google Scholar]
  8. Chan J., Nakabayashi H., Wong N. C. HNF-4 increases activity of the rat Apo A1 gene. Nucleic Acids Res. 1993 Mar 11;21(5):1205–1211. doi: 10.1093/nar/21.5.1205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chen J. L., Attardi L. D., Verrijzer C. P., Yokomori K., Tjian R. Assembly of recombinant TFIID reveals differential coactivator requirements for distinct transcriptional activators. Cell. 1994 Oct 7;79(1):93–105. doi: 10.1016/0092-8674(94)90403-0. [DOI] [PubMed] [Google Scholar]
  10. Chen W. S., Manova K., Weinstein D. C., Duncan S. A., Plump A. S., Prezioso V. R., Bachvarova R. F., Darnell J. E., Jr 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):2466–2477. doi: 10.1101/gad.8.20.2466. [DOI] [PubMed] [Google Scholar]
  11. Choy B., Green M. R. Eukaryotic activators function during multiple steps of preinitiation complex assembly. Nature. 1993 Dec 9;366(6455):531–536. doi: 10.1038/366531a0. [DOI] [PubMed] [Google Scholar]
  12. Danielian P. S., White R., Lees J. A., Parker M. G. Identification of a conserved region required for hormone dependent transcriptional activation by steroid hormone receptors. EMBO J. 1992 Mar;11(3):1025–1033. doi: 10.1002/j.1460-2075.1992.tb05141.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Duncan S. A., Manova K., Chen W. S., Hoodless P., Weinstein D. C., Bachvarova R. F., Darnell J. E., Jr Expression of transcription factor HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the developing mouse embryo: HNF-4 is a marker for primary endoderm in the implanting blastocyst. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7598–7602. doi: 10.1073/pnas.91.16.7598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Durand B., Saunders M., Gaudon C., Roy B., Losson R., Chambon P. Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element on AF-2 activity. EMBO J. 1994 Nov 15;13(22):5370–5382. doi: 10.1002/j.1460-2075.1994.tb06872.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Elliston J. F., Fawell S. E., Klein-Hitpass L., Tsai S. Y., Tsai M. J., Parker M. G., O'Malley B. W. Mechanism of estrogen receptor-dependent transcription in a cell-free system. Mol Cell Biol. 1990 Dec;10(12):6607–6612. doi: 10.1128/mcb.10.12.6607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fondell J. D., Roy A. L., Roeder R. G. Unliganded thyroid hormone receptor inhibits formation of a functional preinitiation complex: implications for active repression. Genes Dev. 1993 Jul;7(7B):1400–1410. doi: 10.1101/gad.7.7b.1400. [DOI] [PubMed] [Google Scholar]
  18. Fuernkranz H. A., Wang Y., Karathanasis S. K., Mak P. Transcriptional regulation of the apoAI gene by hepatic nuclear factor 4 in yeast. Nucleic Acids Res. 1994 Dec 25;22(25):5665–5671. doi: 10.1093/nar/22.25.5665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Galson D. L., Tsuchiya T., Tendler D. S., Huang L. E., Ren Y., Ogura T., Bunn H. F. The orphan receptor hepatic nuclear factor 4 functions as a transcriptional activator for tissue-specific and hypoxia-specific erythropoietin gene expression and is antagonized by EAR3/COUP-TF1. Mol Cell Biol. 1995 Apr;15(4):2135–2144. doi: 10.1128/mcb.15.4.2135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ge H., Roeder R. G. Purification, cloning, and characterization of a human coactivator, PC4, that mediates transcriptional activation of class II genes. Cell. 1994 Aug 12;78(3):513–523. doi: 10.1016/0092-8674(94)90428-6. [DOI] [PubMed] [Google Scholar]
  21. Ge R., Rhee M., Malik S., Karathanasis S. K. Transcriptional repression of apolipoprotein AI gene expression by orphan receptor ARP-1. J Biol Chem. 1994 May 6;269(18):13185–13192. [PubMed] [Google Scholar]
  22. Ginsburg G. S., Ozer J., Karathanasis S. K. Intestinal apolipoprotein AI gene transcription is regulated by multiple distinct DNA elements and is synergistically activated by the orphan nuclear receptor, hepatocyte nuclear factor 4. J Clin Invest. 1995 Jul;96(1):528–538. doi: 10.1172/JCI118065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Glass C. K. Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers. Endocr Rev. 1994 Jun;15(3):391–407. doi: 10.1210/edrv-15-3-391. [DOI] [PubMed] [Google Scholar]
  24. Green S., Chambon P. Nuclear receptors enhance our understanding of transcription regulation. Trends Genet. 1988 Nov;4(11):309–314. doi: 10.1016/0168-9525(88)90108-4. [DOI] [PubMed] [Google Scholar]
  25. Hall R. K., Sladek F. M., Granner D. K. The orphan receptors COUP-TF and HNF-4 serve as accessory factors required for induction of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids. Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):412–416. doi: 10.1073/pnas.92.2.412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Harnish D. C., Malik S., Karathanasis S. K. Activation of apolipoprotein AI gene transcription by the liver-enriched factor HNF-3. J Biol Chem. 1994 Nov 11;269(45):28220–28226. [PubMed] [Google Scholar]
  27. Hawley D. K., Roeder R. G. Functional steps in transcription initiation and reinitiation from the major late promoter in a HeLa nuclear extract. J Biol Chem. 1987 Mar 15;262(8):3452–3461. [PubMed] [Google Scholar]
  28. Heyman R. A., Mangelsdorf D. J., Dyck J. A., Stein R. B., Eichele G., Evans R. M., Thaller C. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell. 1992 Jan 24;68(2):397–406. doi: 10.1016/0092-8674(92)90479-v. [DOI] [PubMed] [Google Scholar]
  29. Hoffmann A., Roeder R. G. Purification of his-tagged proteins in non-denaturing conditions suggests a convenient method for protein interaction studies. Nucleic Acids Res. 1991 Nov 25;19(22):6337–6338. doi: 10.1093/nar/19.22.6337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Imbalzano A. N., Zaret K. S., Kingston R. E. Transcription factor (TF) IIB and TFIIA can independently increase the affinity of the TATA-binding protein for DNA. J Biol Chem. 1994 Mar 18;269(11):8280–8286. [PubMed] [Google Scholar]
  31. Ing N. H., Beekman J. M., Tsai S. Y., Tsai M. J., O'Malley B. W. Members of the steroid hormone receptor superfamily interact with TFIIB (S300-II). J Biol Chem. 1992 Sep 5;267(25):17617–17623. [PubMed] [Google Scholar]
  32. Jacq X., Brou C., Lutz Y., Davidson I., Chambon P., Tora L. Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor. Cell. 1994 Oct 7;79(1):107–117. doi: 10.1016/0092-8674(94)90404-9. [DOI] [PubMed] [Google Scholar]
  33. Jiang G., Nepomuceno L., Hopkins K., Sladek F. M. Exclusive homodimerization of the orphan receptor hepatocyte nuclear factor 4 defines a new subclass of nuclear receptors. Mol Cell Biol. 1995 Sep;15(9):5131–5143. doi: 10.1128/mcb.15.9.5131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Kennelly P. J., Krebs E. G. Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases. J Biol Chem. 1991 Aug 25;266(24):15555–15558. [PubMed] [Google Scholar]
  35. Kim Y. J., Björklund S., Li Y., Sayre M. H., Kornberg R. D. A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II. Cell. 1994 May 20;77(4):599–608. doi: 10.1016/0092-8674(94)90221-6. [DOI] [PubMed] [Google Scholar]
  36. Koleske A. J., Young R. A. An RNA polymerase II holoenzyme responsive to activators. Nature. 1994 Mar 31;368(6470):466–469. doi: 10.1038/368466a0. [DOI] [PubMed] [Google Scholar]
  37. Kuo C. J., Conley P. B., Chen L., Sladek F. M., Darnell J. E., Jr, Crabtree G. R. A transcriptional hierarchy involved in mammalian cell-type specification. Nature. 1992 Jan 30;355(6359):457–461. doi: 10.1038/355457a0. [DOI] [PubMed] [Google Scholar]
  38. Ladias J. A., Karathanasis S. K. Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily. Science. 1991 Feb 1;251(4993):561–565. doi: 10.1126/science.1899293. [DOI] [PubMed] [Google Scholar]
  39. Lai E., Darnell J. E., Jr Transcriptional control in hepatocytes: a window on development. Trends Biochem Sci. 1991 Nov;16(11):427–430. doi: 10.1016/0968-0004(91)90169-v. [DOI] [PubMed] [Google Scholar]
  40. Le Goff P., Montano M. M., Schodin D. J., Katzenellenbogen B. S. Phosphorylation of the human estrogen receptor. Identification of hormone-regulated sites and examination of their influence on transcriptional activity. J Biol Chem. 1994 Feb 11;269(6):4458–4466. [PubMed] [Google Scholar]
  41. Lee S., Hahn S. Model for binding of transcription factor TFIIB to the TBP-DNA complex. Nature. 1995 Aug 17;376(6541):609–612. doi: 10.1038/376609a0. [DOI] [PubMed] [Google Scholar]
  42. Lehmann J. M., Moore L. B., Smith-Oliver T. A., Wilkison W. O., Willson T. M., Kliewer S. A. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem. 1995 Jun 2;270(22):12953–12956. doi: 10.1074/jbc.270.22.12953. [DOI] [PubMed] [Google Scholar]
  43. Lewin B. Commitment and activation at pol II promoters: a tail of protein-protein interactions. Cell. 1990 Jun 29;61(7):1161–1164. doi: 10.1016/0092-8674(90)90675-5. [DOI] [PubMed] [Google Scholar]
  44. Lin Y. S., Green M. R. Mechanism of action of an acidic transcriptional activator in vitro. Cell. 1991 Mar 8;64(5):971–981. doi: 10.1016/0092-8674(91)90321-o. [DOI] [PubMed] [Google Scholar]
  45. MacDonald P. N., Sherman D. R., Dowd D. R., Jefcoat S. C., Jr, DeLisle R. K. The vitamin D receptor interacts with general transcription factor IIB. J Biol Chem. 1995 Mar 3;270(9):4748–4752. doi: 10.1074/jbc.270.9.4748. [DOI] [PubMed] [Google Scholar]
  46. Maldonado E., Ha I., Cortes P., Weis L., Reinberg D. Factors involved in specific transcription by mammalian RNA polymerase II: role of transcription factors IIA, IID, and IIB during formation of a transcription-competent complex. Mol Cell Biol. 1990 Dec;10(12):6335–6347. doi: 10.1128/mcb.10.12.6335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Maldonado E., Reinberg D. News on initiation and elongation of transcription by RNA polymerase II. Curr Opin Cell Biol. 1995 Jun;7(3):352–361. doi: 10.1016/0955-0674(95)80090-5. [DOI] [PubMed] [Google Scholar]
  48. Malik S., Hisatake K., Sumimoto H., Horikoshi M., Roeder R. G. Sequence of general transcription factor TFIIB and relationships to other initiation factors. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9553–9557. doi: 10.1073/pnas.88.21.9553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Malik S., Karathanasis S. Transcriptional activation by the orphan nuclear receptor ARP-1. Nucleic Acids Res. 1995 May 11;23(9):1536–1543. doi: 10.1093/nar/23.9.1536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Malik S., Lee D. K., Roeder R. G. Potential RNA polymerase II-induced interactions of transcription factor TFIIB. Mol Cell Biol. 1993 Oct;13(10):6253–6259. doi: 10.1128/mcb.13.10.6253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Metzger S., Halaas J. L., Breslow J. L., Sladek F. M. Orphan receptor HNF-4 and bZip protein C/EBP alpha bind to overlapping regions of the apolipoprotein B gene promoter and synergistically activate transcription. J Biol Chem. 1993 Aug 5;268(22):16831–16838. [PubMed] [Google Scholar]
  52. Mietus-Snyder M., Sladek F. M., Ginsburg G. S., Kuo C. F., Ladias J. A., Darnell J. E., Jr, Karathanasis S. K. Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells. Mol Cell Biol. 1992 Apr;12(4):1708–1718. doi: 10.1128/mcb.12.4.1708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Nakajima N., Horikoshi M., Roeder R. G. Factors involved in specific transcription by mammalian RNA polymerase II: purification, genetic specificity, and TATA box-promoter interactions of TFIID. Mol Cell Biol. 1988 Oct;8(10):4028–4040. doi: 10.1128/mcb.8.10.4028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. O'Malley B. W., Conneely O. M. Orphan receptors: in search of a unifying hypothesis for activation. Mol Endocrinol. 1992 Sep;6(9):1359–1361. doi: 10.1210/mend.6.9.1331771. [DOI] [PubMed] [Google Scholar]
  55. Pawson T. Protein-tyrosine kinases. Getting down to specifics. Nature. 1995 Feb 9;373(6514):477–478. doi: 10.1038/373477a0. [DOI] [PubMed] [Google Scholar]
  56. Roberts S. G., Green M. R. Activator-induced conformational change in general transcription factor TFIIB. Nature. 1994 Oct 20;371(6499):717–720. doi: 10.1038/371717a0. [DOI] [PubMed] [Google Scholar]
  57. Roeder R. G. The complexities of eukaryotic transcription initiation: regulation of preinitiation complex assembly. Trends Biochem Sci. 1991 Nov;16(11):402–408. doi: 10.1016/0968-0004(91)90164-q. [DOI] [PubMed] [Google Scholar]
  58. Rottman J. N., Widom R. L., Nadal-Ginard B., Mahdavi V., Karathanasis S. K. A retinoic acid-responsive element in the apolipoprotein AI gene distinguishes between two different retinoic acid response pathways. Mol Cell Biol. 1991 Jul;11(7):3814–3820. doi: 10.1128/mcb.11.7.3814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Roy A. L., Malik S., Meisterernst M., Roeder R. G. An alternative pathway for transcription initiation involving TFII-I. Nature. 1993 Sep 23;365(6444):355–359. doi: 10.1038/365355a0. [DOI] [PubMed] [Google Scholar]
  60. Sastry K. N., Seedorf U., Karathanasis S. K. Different cis-acting DNA elements control expression of the human apolipoprotein AI gene in different cell types. Mol Cell Biol. 1988 Feb;8(2):605–614. doi: 10.1128/mcb.8.2.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Satoh H., Nagae Y., Immenschuh S., Satoh T., Muller-Eberhard U. Identification of a liver preference enhancer element of the rat hemopexin gene and its interaction with nuclear factors. J Biol Chem. 1994 Mar 4;269(9):6851–6858. [PubMed] [Google Scholar]
  62. Sawadogo M., Roeder R. G. Factors involved in specific transcription by human RNA polymerase II: analysis by a rapid and quantitative in vitro assay. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4394–4398. doi: 10.1073/pnas.82.13.4394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Sladek F. M. Orphan receptor HNF-4 and liver-specific gene expression. Receptor. 1993 Fall;3(3):223–232. [PubMed] [Google Scholar]
  64. Sladek F. M., Zhong W. M., Lai E., Darnell J. E., Jr Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev. 1990 Dec;4(12B):2353–2365. doi: 10.1101/gad.4.12b.2353. [DOI] [PubMed] [Google Scholar]
  65. Smith C. A., Bates P., Rivera-Gonzalez R., Gu B., DeLuca N. A. ICP4, the major transcriptional regulatory protein of herpes simplex virus type 1, forms a tripartite complex with TATA-binding protein and TFIIB. J Virol. 1993 Aug;67(8):4676–4687. doi: 10.1128/jvi.67.8.4676-4687.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Tjian R., Maniatis T. Transcriptional activation: a complex puzzle with few easy pieces. Cell. 1994 Apr 8;77(1):5–8. doi: 10.1016/0092-8674(94)90227-5. [DOI] [PubMed] [Google Scholar]
  67. Tsai M. J., O'Malley B. W. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem. 1994;63:451–486. doi: 10.1146/annurev.bi.63.070194.002315. [DOI] [PubMed] [Google Scholar]
  68. Tsai S. Y., Sagami I., Wang H., Tsai M. J., O'Malley B. W. Interactions between a DNA-binding transcription factor (COUP) and a non-DNA binding factor (S300-II). Cell. 1987 Aug 28;50(5):701–709. doi: 10.1016/0092-8674(87)90328-x. [DOI] [PubMed] [Google Scholar]
  69. Wang L. H., Tsai S. Y., Cook R. G., Beattie W. G., Tsai M. J., O'Malley B. W. COUP transcription factor is a member of the steroid receptor superfamily. Nature. 1989 Jul 13;340(6229):163–166. doi: 10.1038/340163a0. [DOI] [PubMed] [Google Scholar]
  70. Xanthopoulos K. G., Mirkovitch J. Gene regulation in rodent hepatocytes during development, differentiation and disease. Eur J Biochem. 1993 Sep 1;216(2):353–360. doi: 10.1111/j.1432-1033.1993.tb18152.x. [DOI] [PubMed] [Google Scholar]
  71. Zhang X. K., Hoffmann B., Tran P. B., Graupner G., Pfahl M. Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors. Nature. 1992 Jan 30;355(6359):441–446. doi: 10.1038/355441a0. [DOI] [PubMed] [Google Scholar]
  72. Zhong W., Mirkovitch J., Darnell J. E., Jr Tissue-specific regulation of mouse hepatocyte nuclear factor 4 expression. Mol Cell Biol. 1994 Nov;14(11):7276–7284. doi: 10.1128/mcb.14.11.7276. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES