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Intronic hormone response elements mediate regulation of FKBP5 by progestins and glucocorticoids.
Cell Stress Chaperones. 2004 Autumn; 9(3):243-52.CS

Abstract

Expression of FKBP51, a large molecular weight immunophilin, is strongly enhanced by glucocorticoids, progestins, and androgens. However, the activity of a 3.4-kb fragment of the FKBP51 gene (FKBP5) promoter was only weakly increased by progestin and we show here that it is unresponsive to glucocorticoids and androgens. The entire FKBP5 was scanned for consensus hormone response elements (HREs) using MatInspector. We found that 2 regions of intron E, which are conserved in rat and mouse FKBP5, contain HRE-like sequences with high match scores. Deoxyribonucleic acid fragments (approximately 1 kb in length) containing these regions were amplified and tested in reporter gene assays for steroid responsiveness. One region of intron E of FKBP5 (pIE2) conferred both glucocorticoid and progestin responsiveness to 2 heterologous reporter genes, whereas the other, less-conserved region of intron E (pIE1) was responsive only to progestins. The inclusion of pIE1 upstream of pIE2 (pIE1IE2) enhanced progestin but not glucocorticoid responsiveness. None of the constructs containing intronic sequences was responsive to androgens. Mutation of the putative HREs within pIE1 and pIE2 eliminated hormone responsiveness. Electrophoretic mobility shift assays demonstrated that progesterone receptors (PR) bound to the HRE in pIE1, whereas both PR and glucocorticoid receptors interacted with the HRE in pIE2. These data suggest that distal intronic elements significantly contribute to transcriptional regulation of FKBP5 by glucocorticoids and progestins.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15544162

Citation

Hubler, Tina R., and Jonathan G. Scammell. "Intronic Hormone Response Elements Mediate Regulation of FKBP5 By Progestins and Glucocorticoids." Cell Stress & Chaperones, vol. 9, no. 3, 2004, pp. 243-52.
Hubler TR, Scammell JG. Intronic hormone response elements mediate regulation of FKBP5 by progestins and glucocorticoids. Cell Stress Chaperones. 2004;9(3):243-52.
Hubler, T. R., & Scammell, J. G. (2004). Intronic hormone response elements mediate regulation of FKBP5 by progestins and glucocorticoids. Cell Stress & Chaperones, 9(3), 243-52.
Hubler TR, Scammell JG. Intronic Hormone Response Elements Mediate Regulation of FKBP5 By Progestins and Glucocorticoids. Cell Stress Chaperones. 2004;9(3):243-52. PubMed PMID: 15544162.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intronic hormone response elements mediate regulation of FKBP5 by progestins and glucocorticoids. AU - Hubler,Tina R, AU - Scammell,Jonathan G, PY - 2004/11/17/pubmed PY - 2005/4/26/medline PY - 2004/11/17/entrez SP - 243 EP - 52 JF - Cell stress & chaperones JO - Cell Stress Chaperones VL - 9 IS - 3 N2 - Expression of FKBP51, a large molecular weight immunophilin, is strongly enhanced by glucocorticoids, progestins, and androgens. However, the activity of a 3.4-kb fragment of the FKBP51 gene (FKBP5) promoter was only weakly increased by progestin and we show here that it is unresponsive to glucocorticoids and androgens. The entire FKBP5 was scanned for consensus hormone response elements (HREs) using MatInspector. We found that 2 regions of intron E, which are conserved in rat and mouse FKBP5, contain HRE-like sequences with high match scores. Deoxyribonucleic acid fragments (approximately 1 kb in length) containing these regions were amplified and tested in reporter gene assays for steroid responsiveness. One region of intron E of FKBP5 (pIE2) conferred both glucocorticoid and progestin responsiveness to 2 heterologous reporter genes, whereas the other, less-conserved region of intron E (pIE1) was responsive only to progestins. The inclusion of pIE1 upstream of pIE2 (pIE1IE2) enhanced progestin but not glucocorticoid responsiveness. None of the constructs containing intronic sequences was responsive to androgens. Mutation of the putative HREs within pIE1 and pIE2 eliminated hormone responsiveness. Electrophoretic mobility shift assays demonstrated that progesterone receptors (PR) bound to the HRE in pIE1, whereas both PR and glucocorticoid receptors interacted with the HRE in pIE2. These data suggest that distal intronic elements significantly contribute to transcriptional regulation of FKBP5 by glucocorticoids and progestins. SN - 1355-8145 UR - https://www.unboundmedicine.com/medline/citation/15544162/Intronic_hormone_response_elements_mediate_regulation_of_FKBP5_by_progestins_and_glucocorticoids_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/15544162/ DB - PRIME DP - Unbound Medicine ER -