• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of embojLink to Publisher's site
EMBO J. Sep 1991; 10(9): 2513–2521.
PMCID: PMC452948

Interference and synergism of glucocorticoid receptor and octamer factors.

Abstract

We have analysed the interplay of glucocorticoid receptor (GR) and the lymphocyte-specific factor Oct-2A with transient co-transfection assays. Our data confirm our previously described observation that GR and the apparently unrelated factors belonging to the Octamer family can synergize when permitted to bind in cis. However, when GR binding sites are not present in the reporter genes, we observe that the action of the cloned factor Oct-2A expressed in HeLa cells is strongly inhibited in the presence of active GR molecules. We can demonstrate that this GR-mediated inhibition of Oct-2A action is neither due to competitive binding to DNA target sites nor to a reduction of DNA binding competent Oct-2A in the transfected cells. We observe that the phenomenon is not reciprocal, since co-expression of Oct-2A does not inhibit GR-dependent transcription activation. Furthermore, we provide evidence that the observed GR-Oct-2A interference may be dependent on the type of cell line hosting the co-transfected molecules. We consider it likely that the GR-mediated inhibition is due to the exhaustion of some rate-limiting co-activators.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Banerji J, Rusconi S, Schaffner W. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell. 1981 Dec;27(2 Pt 1):299–308. [PubMed]
  • Barberis A, Superti-Furga G, Busslinger M. Mutually exclusive interaction of the CCAAT-binding factor and of a displacement protein with overlapping sequences of a histone gene promoter. Cell. 1987 Jul 31;50(3):347–359. [PubMed]
  • Beato M. Gene regulation by steroid hormones. Cell. 1989 Feb 10;56(3):335–344. [PubMed]
  • Berger SL, Cress WD, Cress A, Triezenberg SJ, Guarente L. Selective inhibition of activated but not basal transcription by the acidic activation domain of VP16: evidence for transcriptional adaptors. Cell. 1990 Jun 29;61(7):1199–1208. [PubMed]
  • Boshart M, Weber F, Jahn G, Dorsch-Häsler K, Fleckenstein B, Schaffner W. A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell. 1985 Jun;41(2):521–530. [PubMed]
  • Brüggemeier U, Kalff M, Franke S, Scheidereit C, Beato M. Ubiquitous transcription factor OTF-1 mediates induction of the MMTV promoter through synergistic interaction with hormone receptors. Cell. 1991 Feb 8;64(3):565–572. [PubMed]
  • Courey AJ, Tjian R. Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif. Cell. 1988 Dec 2;55(5):887–898. [PubMed]
  • Drouin J, Trifiro MA, Plante RK, Nemer M, Eriksson P, Wrange O. Glucocorticoid receptor binding to a specific DNA sequence is required for hormone-dependent repression of pro-opiomelanocortin gene transcription. Mol Cell Biol. 1989 Dec;9(12):5305–5314. [PMC free article] [PubMed]
  • Freedman LP, Luisi BF, Korszun ZR, Basavappa R, Sigler PB, Yamamoto KR. The function and structure of the metal coordination sites within the glucocorticoid receptor DNA binding domain. Nature. 1988 Aug 11;334(6182):543–546. [PubMed]
  • Gerster T, Matthias P, Thali M, Jiricny J, Schaffner W. Cell type-specificity elements of the immunoglobulin heavy chain gene enhancer. EMBO J. 1987 May;6(5):1323–1330. [PMC free article] [PubMed]
  • Gerster T, Balmaceda CG, Roeder RG. The cell type-specific octamer transcription factor OTF-2 has two domains required for the activation of transcription. EMBO J. 1990 May;9(5):1635–1643. [PMC free article] [PubMed]
  • Giguère V, Hollenberg SM, Rosenfeld MG, Evans RM. Functional domains of the human glucocorticoid receptor. Cell. 1986 Aug 29;46(5):645–652. [PubMed]
  • Gill G, Ptashne M. Negative effect of the transcriptional activator GAL4. Nature. 1988 Aug 25;334(6184):721–724. [PubMed]
  • Himmelfarb HJ, Pearlberg J, Last DH, Ptashne M. GAL11P: a yeast mutation that potentiates the effect of weak GAL4-derived activators. Cell. 1990 Dec 21;63(6):1299–1309. [PubMed]
  • Hollenberg SM, Evans RM. Multiple and cooperative trans-activation domains of the human glucocorticoid receptor. Cell. 1988 Dec 2;55(5):899–906. [PubMed]
  • Johnson PF, McKnight SL. Eukaryotic transcriptional regulatory proteins. Annu Rev Biochem. 1989;58:799–839. [PubMed]
  • Jonat C, Rahmsdorf HJ, Park KK, Cato AC, Gebel S, Ponta H, Herrlich P. Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell. 1990 Sep 21;62(6):1189–1204. [PubMed]
  • Kelleher RJ, 3rd, Flanagan PM, Kornberg RD. A novel mediator between activator proteins and the RNA polymerase II transcription apparatus. Cell. 1990 Jun 29;61(7):1209–1215. [PubMed]
  • Kemler I, Schaffner W. Octamer transcription factors and the cell type-specificity of immunoglobulin gene expression. FASEB J. 1990 Mar;4(5):1444–1449. [PubMed]
  • Kemler I, Bucher E, Seipel K, Müller-Immerglück MM, Schaffner W. Promoters with the octamer DNA motif (ATGCAAAT) can be ubiquitous or cell type-specific depending on binding affinity of the octamer site and Oct-factor concentration. Nucleic Acids Res. 1991 Jan 25;19(2):237–242. [PMC free article] [PubMed]
  • Klock G, Strähle U, Schütz G. Oestrogen and glucocorticoid responsive elements are closely related but distinct. Nature. 1987 Oct 22;329(6141):734–736. [PubMed]
  • Lucibello FC, Slater EP, Jooss KU, Beato M, Müller R. Mutual transrepression of Fos and the glucocorticoid receptor: involvement of a functional domain in Fos which is absent in FosB. EMBO J. 1990 Sep;9(9):2827–2834. [PMC free article] [PubMed]
  • Ma J, Ptashne M. Deletion analysis of GAL4 defines two transcriptional activating segments. Cell. 1987 Mar 13;48(5):847–853. [PubMed]
  • Mermod N, O'Neill EA, Kelly TJ, Tjian R. The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain. Cell. 1989 Aug 25;58(4):741–753. [PubMed]
  • Meyer ME, Gronemeyer H, Turcotte B, Bocquel MT, Tasset D, Chambon P. Steroid hormone receptors compete for factors that mediate their enhancer function. Cell. 1989 May 5;57(3):433–442. [PubMed]
  • Mitchell PJ, Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. [PubMed]
  • Müller MM, Gerster T, Schaffner W. Enhancer sequences and the regulation of gene transcription. Eur J Biochem. 1988 Oct 1;176(3):485–495. [PubMed]
  • Müller MM, Ruppert S, Schaffner W, Matthias P. A cloned octamer transcription factor stimulates transcription from lymphoid-specific promoters in non-B cells. Nature. 1988 Dec 8;336(6199):544–551. [PubMed]
  • Müller MM, Schreiber E, Schaffner W, Matthias P. Rapid test for in vivo stability and DNA binding of mutated octamer binding proteins with 'mini-extracts' prepared from transfected cells. Nucleic Acids Res. 1989 Aug 11;17(15):6420–6420. [PMC free article] [PubMed]
  • Müller-Immerglück MM, Schaffner W, Matthias P. Transcription factor Oct-2A contains functionally redundant activating domains and works selectively from a promoter but not from a remote enhancer position in non-lymphoid (HeLa) cells. EMBO J. 1990 May;9(5):1625–1634. [PMC free article] [PubMed]
  • Nishizawa M, Suzuki Y, Nogi Y, Matsumoto K, Fukasawa T. Yeast Gal11 protein mediates the transcriptional activation signal of two different transacting factors, Gal4 and general regulatory factor I/repressor/activator site binding protein 1/translation upstream factor. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5373–5377. [PMC free article] [PubMed]
  • Oro AE, Hollenberg SM, Evans RM. Transcriptional inhibition by a glucocorticoid receptor-beta-galactosidase fusion protein. Cell. 1988 Dec 23;55(6):1109–1114. [PubMed]
  • Päbo S, Weber F, Kämpe O, Schaffner W, Peterson PA. Association between transplantation antigens and a viral membrane protein synthesized from a mammalian expression vector. Cell. 1983 Jun;33(2):445–453. [PubMed]
  • Peterson MG, Tanese N, Pugh BF, Tjian R. Functional domains and upstream activation properties of cloned human TATA binding protein. Science. 1990 Jun 29;248(4963):1625–1630. [PubMed]
  • Picard D, Yamamoto KR. Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor. EMBO J. 1987 Nov;6(11):3333–3340. [PMC free article] [PubMed]
  • Ptashne M. How eukaryotic transcriptional activators work. Nature. 1988 Oct 20;335(6192):683–689. [PubMed]
  • Ptashne M, Gann AA. Activators and targets. Nature. 1990 Jul 26;346(6282):329–331. [PubMed]
  • Rusconi S, Yamamoto KR. Functional dissection of the hormone and DNA binding activities of the glucocorticoid receptor. EMBO J. 1987 May;6(5):1309–1315. [PMC free article] [PubMed]
  • Rusconi S, Severne Y, Georgiev O, Galli I, Wieland S. A novel expression assay to study transcriptional activators. Gene. 1990 May 14;89(2):211–221. [PubMed]
  • Schreiber E, Matthias P, Müller MM, Schaffner W. Identification of a novel lymphoid specific octamer binding protein (OTF-2B) by proteolytic clipping bandshift assay (PCBA). EMBO J. 1988 Dec 20;7(13):4221–4229. [PMC free article] [PubMed]
  • Schreiber E, Matthias P, Müller MM, Schaffner W. Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. Nucleic Acids Res. 1989 Aug 11;17(15):6419–6419. [PMC free article] [PubMed]
  • Schüle R, Muller M, Kaltschmidt C, Renkawitz R. Many transcription factors interact synergistically with steroid receptors. Science. 1988 Dec 9;242(4884):1418–1420. [PubMed]
  • Schüle R, Rangarajan P, Kliewer S, Ransone LJ, Bolado J, Yang N, Verma IM, Evans RM. Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell. 1990 Sep 21;62(6):1217–1226. [PubMed]
  • Schwartzman RA, Cidlowski JA. Internucleosomal deoxyribonucleic acid cleavage activity in apoptotic thymocytes: detection and endocrine regulation. Endocrinology. 1991 Feb;128(2):1190–1197. [PubMed]
  • Severne Y, Wieland S, Schaffner W, Rusconi S. Metal binding 'finger' structures in the glucocorticoid receptor defined by site-directed mutagenesis. EMBO J. 1988 Aug;7(8):2503–2508. [PMC free article] [PubMed]
  • Stern S, Tanaka M, Herr W. The Oct-1 homoeodomain directs formation of a multiprotein-DNA complex with the HSV transactivator VP16. Nature. 1989 Oct 19;341(6243):624–630. [PubMed]
  • Stringer KF, Ingles CJ, Greenblatt J. Direct and selective binding of an acidic transcriptional activation domain to the TATA-box factor TFIID. Nature. 1990 Jun 28;345(6278):783–786. [PubMed]
  • Sturm RA, Das G, Herr W. The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. Genes Dev. 1988 Dec;2(12A):1582–1599. [PubMed]
  • Tasset D, Tora L, Fromental C, Scheer E, Chambon P. Distinct classes of transcriptional activating domains function by different mechanisms. Cell. 1990 Sep 21;62(6):1177–1187. [PubMed]
  • Thali M, Rusconi S, Schaffner W. Immediate early protein of pseudorabies virus is a general transactivator but stimulates only suboptimally utilized promoters. A clue to specificity? J Mol Biol. 1990 Sep 20;215(2):301–311. [PubMed]
  • Tora L, White J, Brou C, Tasset D, Webster N, Scheer E, Chambon P. The human estrogen receptor has two independent nonacidic transcriptional activation functions. Cell. 1989 Nov 3;59(3):477–487. [PubMed]
  • Westin G, Gerster T, Müller MM, Schaffner G, Schaffner W. OVEC, a versatile system to study transcription in mammalian cells and cell-free extracts. Nucleic Acids Res. 1987 Sep 11;15(17):6787–6798. [PMC free article] [PubMed]
  • Wieland S, Schatt MD, Rusconi S. Role of TATA-element in transcription from glucocorticoid receptor-responsive model promoters. Nucleic Acids Res. 1990 Sep 11;18(17):5113–5118. [PMC free article] [PubMed]
  • Wirth T, Priess A, Annweiler A, Zwilling S, Oeler B. Multiple Oct2 isoforms are generated by alternative splicing. Nucleic Acids Res. 1991 Jan 11;19(1):43–51. [PMC free article] [PubMed]
  • Yamamoto KR. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. [PubMed]
  • Yang-Yen HF, Chambard JC, Sun YL, Smeal T, Schmidt TJ, Drouin J, Karin M. 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):1205–1215. [PubMed]
  • Ruvkun G, Finney M. Regulation of transcription and cell identity by POU domain proteins. Cell. 1991 Feb 8;64(3):475–478. [PubMed]
  • Schatt MD, Rusconi S, Schaffner W. A single DNA-binding transcription factor is sufficient for activation from a distant enhancer and/or from a promoter position. EMBO J. 1990 Feb;9(2):481–487. [PMC free article] [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...