論文

査読有り
2019年7月29日

Aryl Hydrocarbon Receptor Directly Regulates Artemin Gene Expression

Molecular and Cellular Biology
  • Tomohiro Edamitsu
  • ,
  • Keiko Taguchi
  • ,
  • Eri H. Kobayashi
  • ,
  • Ryuhei Okuyama
  • ,
  • Masayuki Yamamoto

39
20
記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1128/mcb.00190-19
出版者・発行元
American Society for Microbiology

<title>ABSTRACT</title>
Transgenic mice expressing a constitutively active form of the aryl hydrocarbon receptor in keratinocytes (AhR-CA mice) develop severe dermatitis that substantially recapitulates the pathology of human atopic dermatitis. The neurotrophic factor artemin (Artn) is highly expressed in the epidermis of AhR-CA mice and causes hypersensitivity to itch (alloknesis) by elongating nerves into the epidermis. However, whether the <italic>Artn</italic> gene is regulated directly by AhR or indirectly through complex regulation associated with AhR remains unclear. To this end, we previously conducted chromatin immunoprecipitation-sequencing analyses of the <italic>Artn</italic> locus and found a xenobiotic response element (XRE) motif located far upstream (52 kb) of the gene. Therefore, in this study, we addressed whether the XRE actually regulates the <italic>Artn</italic> gene expression by deleting the region containing the motif. We generated two lines of ArtnΔXRE mice. In the mouse epidermis, inducible expression of the <italic>Artn</italic> gene by the AhR agonist 3-methylcholanthrene was substantially suppressed compared to that in wild-type mice. Importantly, in AhR-CA::ArtnΔXRE mice, <italic>Artn</italic> expression was significantly suppressed, and alloknesis was improved. These results demonstrate that the <italic>Artn</italic> gene is indeed regulated by the distal XRE-containing enhancer, and alloknesis in AhR-CA mice is provoked by the AhR-mediated direct induction of the <italic>Artn</italic> gene.

リンク情報
DOI
https://doi.org/10.1128/mcb.00190-19
URL
https://syndication.highwire.org/content/doi/10.1128/MCB.00190-19
ID情報
  • DOI : 10.1128/mcb.00190-19
  • ISSN : 0270-7306
  • eISSN : 1098-5549

エクスポート
BibTeX RIS