Glucocorticoids regulate the expression of the stressprotein alpha B-crystallin.
alpha B-crystallin is a major component of the eye lens but is also found in many extralenticular tissues. In established fibroblasts it is synthesized in response to stress such as hyperthermia. Here we report that the treatment of NIH3T3 fibroblasts with the synthetic glucocorticoid hormone dexamethasone resulted in the accumulation of substantial amounts of alpha B-crystallin, alpha B-crystallin mRNA accumulated slowly and over a period of many days in response to prolonged hormone treatment. alpha B-crystallin promoter-reporter constructs were hormone responsive. A putative glucocorticoid response element (GRE) within the analysed promoter region could bind the glucocorticoid receptor as revealed from in vitro footprint analysis but is not involved in the hormone-mediated gene activation. Deletions of 5' flanking regions to position -465 relative to the transcription start allowed for full hormone responsiveness. A deletion from -465 to -389 abolish hormone-mediated gene induction. No sequence element closely resembling a classical GRE is present within that hormone-responsive region.
Scheier
B
B
Department of Pathology, University Hospital, Zürich, Switzerland.
Foletti
A
A
Stark
G
G
Aoyama
A
A
Döbbeling
U
U
Rusconi
S
S
Klemenz
R
R
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D003459:Crystallins / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D016415:Sequence Alignment; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation
D003459:Crystallins; D003907:Dexamethasone