KMID : 0381120110330010083
|
|
Genes and Genomics 2011 Volume.33 No. 1 p.83 ~ p.88
|
|
Retinoic acid induces expression of Ig germ line ¥á transcript, an IgA isotype switching indicative, through retinoic acid receptor
|
|
Park Mi-Hee
Park Seok-Rae Lee Mi-Ra Kim Young-Ha Kim Pyeung-Hyeun
|
|
Abstract
|
|
|
Retinoic acid (RA) is considered to possess an activity of IgA isotype switching. Thus far, TGF-¥â1 is known to be the most powerful IgA isotype switch factor. To elucidate the molecular mechanisms underlying the Ig germ line (GL) ¥á transcriptional regulation by RA, we constructed three different sizes of mouse GL¥á promoter reporters; short-GL¥á(?130/+14), middle-GL¥á(?448/+72) and long-GL¥á(?3028/+72). Based on luciferase assay, RA increased the activity of all three GL¥á promoter reporters by approximately 2-fold and the effect was further enhanced by TGF-¥â1. Overexpression of Smad3/4 increased TGF-¥â1-induced GL¥á promoter activities but had no effect on RA-induced GL¥á promoter activities. In order to analyze the characteristics of the RA-inducible GL¥á promoter region, we also constructed two mutant reporters: Smad3 binding elements (SBEs)-substituted short-GL¥á (short-GL¥á mSBE) and Runx3 binding elements (RBEs)-substituted short-GL¥á (short-GL¥á mRBE) promoter reporters. Promoter activities of the two mutant reporters to RA were comparable to that of wild type reporter, while those of the two mutant reporters to TGF-¥â1 were markedly diminished as compared to that of WT short-GL¥á. Finally, RA-induced GL¥á transcription was virtually disappeared by LE540, an antagonist of RA receptor (RAR). Taken together, these results suggest that RA induces GL¥á transcription mainly through RAR pathway, where neither Smad3/4 nor Runx3 is involved.
|
|
KEYWORD
|
|
Retinoic acid TGF-¥â1 GL¥á promoter IgA Smad RA receptor
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|