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


OBJECTIVE
GRalpha has roles in both transcriptional activation and repression. We wished to determine the influence of GRbeta 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 GRbeta has repressive activity on the promoters of the human IL5 and IL13 genes.


RESULTS
GRbeta is able to act as a transcriptional repressor of cytokine genes and mediates its function through the recruitment of histone deacetylase complexes.


CONCLUSIONS
GRalpha and GRbeta act in a similar manner on IL5 and IL13 promoters, serving to repress transcription. In this circumstance GRbeta does not act as a dominant-negative inhibitor of GRalpha.
Kelly
Audrey
A
Kings College London, Medical Research Council/Asthma UK Centre in Allergic Mechanisms of Asthma, Guy's Hospital, London, United Kingdom.
Bowen
Holly
H
Jee
Young-Koo
YK
Mahfiche
Nabila
N
Soh
Cecilia
C
Lee
Tak
T
Hawrylowicz
Catherine
C
Lavender
Paul
P
D002460:Cell Line; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D018793:Interleukin-13; D015848:Interleukin-5; D011965:Receptors, Glucocorticoid; C121943:glucocorticoid receptor beta; D006655:Histone Deacetylases