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Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions.

Publication ,  Journal Article
Tzukerman, MT; Esty, A; Santiso-Mere, D; Danielian, P; Parker, MG; Stein, RB; Pike, JW; McDonnell, DP
Published in: Mol Endocrinol
January 1994

We have used a series of human estrogen receptor (ER) mutants to evaluate the cell- and promoter-specific transcriptional activities of the TAF1 and TAF2 transactivation regions within the human ER. We show that the manifestation of TAF1 or TAF2 function depends strongly upon promoter context; on certain promoters, both the TAF1 and TAF2 activators are required for wild-type transcriptional activity, whereas on other promoters, the TAF1 and TAF2 activators function independently. Using these constructs, we show that the antagonist activity of the triphenylethylene-derived antiestrogens, e.g. tamoxifen, arises from their intrinsic inability to activate ER TAF2 function. However, on certain promoters, these antiestrogens efficiently activate gene transcription through ER. Consistent with this observation, the TAF2 function of the ER is not required on all promoters. In these TAF2-independent promoter contexts, TAF2 function may be provided by a separate transcription factor bound to the promoter. These data suggest that 1) TAF1 may be the major transcriptional activator of the ER; and 2) TAF2 functions as a transcriptional facilitator. On promoters where TAF2 function is provided independently of the ER, the TAF1 function of the ER can function independently of TAF2 activity, allowing triphenylethylene-derived antiestrogens to demonstrate partial agonist activity. These observations provide a possible molecular explanation for the tissue-specific partial agonist properties of tamoxifen and related triphenylethylene antiestrogens observed in vivo.

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Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

January 1994

Volume

8

Issue

1

Start / End Page

21 / 30

Location

United States

Related Subject Headings

  • Transfection
  • Transcriptional Activation
  • Transcription, Genetic
  • Tamoxifen
  • Recombinant Proteins
  • Receptors, Estrogen
  • Promoter Regions, Genetic
  • Mutation
  • Humans
  • Endocrinology & Metabolism
 

Citation

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Tzukerman, M. T., Esty, A., Santiso-Mere, D., Danielian, P., Parker, M. G., Stein, R. B., … McDonnell, D. P. (1994). Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions. Mol Endocrinol, 8(1), 21–30. https://doi.org/10.1210/mend.8.1.8152428
Tzukerman, M. T., A. Esty, D. Santiso-Mere, P. Danielian, M. G. Parker, R. B. Stein, J. W. Pike, and D. P. McDonnell. “Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions.Mol Endocrinol 8, no. 1 (January 1994): 21–30. https://doi.org/10.1210/mend.8.1.8152428.
Tzukerman MT, Esty A, Santiso-Mere D, Danielian P, Parker MG, Stein RB, et al. Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions. Mol Endocrinol. 1994 Jan;8(1):21–30.
Tzukerman, M. T., et al. “Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions.Mol Endocrinol, vol. 8, no. 1, Jan. 1994, pp. 21–30. Pubmed, doi:10.1210/mend.8.1.8152428.
Tzukerman MT, Esty A, Santiso-Mere D, Danielian P, Parker MG, Stein RB, Pike JW, McDonnell DP. Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions. Mol Endocrinol. 1994 Jan;8(1):21–30.

Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

January 1994

Volume

8

Issue

1

Start / End Page

21 / 30

Location

United States

Related Subject Headings

  • Transfection
  • Transcriptional Activation
  • Transcription, Genetic
  • Tamoxifen
  • Recombinant Proteins
  • Receptors, Estrogen
  • Promoter Regions, Genetic
  • Mutation
  • Humans
  • Endocrinology & Metabolism