The first exon of the human sc gene contains an androgen responsive unit and an interferon regulatory factor element.
Secretory component (SC) plays a key role in the transport of IgA and IgM to the lumina of many glands. The gene is constitutively expressed, but can be modulated by hormonal and immunological stimuli. Recently, the promoter and the first exon of the human sc gene have been cloned. The first exon contains a putative androgen/glucocorticoid response element (ARE/GRE) and an Interferon Regulatory Factor Element (IRF-E). Here we show that the ARE/GRE can bind the DNA-binding domain (DBD) of both the androgen (AR) and glucocorticoid receptor (GR) with a preference for the AR-DBD. In transient transfection experiments, this element confers higher responsiveness to androgens than to glucocorticoids. The IRF-E can function as an IRF-2, but surprisingly not as an IRF-I responsive element. We postulate that these two regulatory elements play a key role in the complex regulation of the sc gene in vivo.
Haelens
A
A
Division of Biochemistry, Faculty of Medicine, University of Leuven, Belgium.
Verrijdt
G
G
Schoenmakers
E
E
Alen
P
P
Peeters
B
B
Rombauts
W
W
Claessens
F
F
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D005091:Exons; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D020218:Response Elements; D012635:Secretory Component / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000728:Androgens; D005938:Glucocorticoids; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D012635:Secretory Component; D004247:DNA; D007372:Interferons