The glucocorticoid receptor beta isoform can mediate transcriptional repression by recruiting histone deacetylases

TY - JOUR

T1 - The glucocorticoid receptor beta isoform can mediate transcriptional repression by recruiting histone deacetylases

AU - Kelly, A

AU - Bowen, H

AU - Jee, Y K

AU - Mahfiche, N

AU - Soh, C

AU - Lee, T

AU - Hawrylowicz, C

AU - Lavender, P

PY - 2008/1

Y1 - 2008/1

N2 - Background: The glucocorticoid receptor (GR) is able to participate in regulation of transcription by a variety of mechanisms, one of which involves DNA binding and recruitment of regulatory cofactors. The best-studied forms of the receptor are the 777-amino-acid alpha and the 742-amino-acid beta variants. The beta isoform, which does not bind cortisol in human subjects, has been proposed to be a dominant-negative inhibitor of the transcriptional activation-competent GR alpha isoform. Objective: GR alpha has roles in both transcriptional activation and repression. We wished to determine the influence of GR beta on genes that are normally transcriptionally repressed by glucocorticoids. We studied IL5 and IL13, which both contribute to the asthmatic phenotype. Methods: We used transient transfection systems and coimmunoprecipitation experiments to determine whether GR beta has repressive activity on the promoters of the human IL5 and IL13 genes. Results: GRP is able to act as a transcriptional repressor of cytokine genes and mediates its function through the recruitment of histone deacetylase complexes. Conclusion: GR alpha and GR beta act in a similar manner on IL5 and IL13 promoters, serving to repress transcription. In this circumstance GR beta does not act as a dominant-negative inhibitor of GR alpha

AB - Background: The glucocorticoid receptor (GR) is able to participate in regulation of transcription by a variety of mechanisms, one of which involves DNA binding and recruitment of regulatory cofactors. The best-studied forms of the receptor are the 777-amino-acid alpha and the 742-amino-acid beta variants. The beta isoform, which does not bind cortisol in human subjects, has been proposed to be a dominant-negative inhibitor of the transcriptional activation-competent GR alpha isoform. Objective: GR alpha has roles in both transcriptional activation and repression. We wished to determine the influence of GR beta on genes that are normally transcriptionally repressed by glucocorticoids. We studied IL5 and IL13, which both contribute to the asthmatic phenotype. Methods: We used transient transfection systems and coimmunoprecipitation experiments to determine whether GR beta has repressive activity on the promoters of the human IL5 and IL13 genes. Results: GRP is able to act as a transcriptional repressor of cytokine genes and mediates its function through the recruitment of histone deacetylase complexes. Conclusion: GR alpha and GR beta act in a similar manner on IL5 and IL13 promoters, serving to repress transcription. In this circumstance GR beta does not act as a dominant-negative inhibitor of GR alpha

U2 - 10.1016/j.jaci.2007.09.010

DO - 10.1016/j.jaci.2007.09.010

M3 - Article

SN - 1097-6825

VL - 121

SP - 203 - 208.e1

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 1

ER -