| First Author | Liu S | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 4 | Pages | e17904 |
| PubMed ID | 21494593 | Mgi Jnum | J:172222 |
| Mgi Id | MGI:5005013 | Doi | 10.1371/journal.pone.0017904 |
| Citation | Liu S, et al. (2011) Regulation of mouse small heat shock protein alphab-crystallin gene by aryl hydrocarbon receptor. PLoS One 6(4):e17904 |
| abstractText | The stress-inducible small heat shock protein (shsp)/alphaB-crystallin gene is expressed highly in the lens and moderately in other tissues. Here we provide evidence that it is a target gene of the aryl hydrocarbon receptor (AhR) transcription factor. A sequence (-329/-323, CATGCGA) similar to the consensus xenobiotic responsive element (XRE), called here XRE-like, is present in the alphaBE2 region of alphaB-crystallin enhancer and can bind AhR in vitro and in vivo. alphaB-crystallin protein levels were reduced in retina, lens, cornea, heart, skeletal muscle and cultured muscle fibroblasts of AhR(-/-) mice; alphaB-crystallin mRNA levels were reduced in the eye, heart and skeletal muscle of AhR(-/-) mice. Increased AhR stimulated alphaB-crystallin expression in transfection experiments conducted in conjunction with the aryl hydrocarbon receptor nuclear translocator (ARNT) and decreased AhR reduced alphaB-crystallin expression. AhR effect on aB-crystallin promoter activity was cell-dependent in transfection experiments. AhR up-regulated alphaB-crystallin promoter activity in transfected HeLa, NIH3T3 and COS-7 cells in the absence of exogenously added ligand (TCDD), but had no effect on the alphaB-crystallin promoter in C(2)C(12), CV-1 or Hepa-1 cells with or without TCDD. TCDD enhanced AhR-stimulated alphaB-crystallin promoter activity in transfected alphaTN4 cells. AhR could bind to an XRE-like site in the alphaB-crystallin enhancer in vitro and in vivo. Finally, site-specific mutagenesis experiments showed that the XRE-like motif was necessary for both basal and maximal AhR-induction of alphaB-crystallin promoter activity. Our data strongly suggest that AhR is a regulator of alphaB-crystallin gene expression and provide new avenues of research for the mechanism of tissue-specific alphaB-crystallin gene regulation under normal and physiologically stressed conditions. |
