title: Involvement of PU.1 in mast cell/basophil-specific function of the human IL1RL1/ST2 promoter.
abstract: BACKGROUND
  The human IL1RL1/ST2 gene encodes IL33 receptor. Recently, IL33 has been recognized as a key molecule for the development of Th2 response. Although mast cells and basophils are major targets of IL33 and play important roles in IL33-mediated Th2-type immune responses, the expression mechanism of ST2 in mast cells and basophils is largely unknown. In the present study, we analyzed regulation mechanism of the human ST2 promoter in the human mast cell line LAD2 and basophilic cell line KU812.
  
  
  METHODS
  Promoter activity was determined by reporter assay with plasmids carrying the wild-type ST2 promoter obtained from human genomic DNA and its mutant. The transcription factor binding to the identified cis-element was identified by an electrophoretic mobility shift assay (EMSA). The effect of candidate transcription factor on ST2 expression was confirmed by analyzing ST2 mRNA level in siRNA-introduced cells.
  
  
  RESULTS
  Reporter assay demonstrated that a cis-element of typical Ets-family binding sequence was critical for promoter activity in LAD2 and KU812. An Ets-family transcription factor PU.1 bound to this element in an EMSA. When PU.1 expression was suppressed by siRNA, ST2 mRNA level was significantly reduced in KU812.
  
  
  CONCLUSIONS
  These observations indicated that PU.1 positively regulates the ST2 promoter as a transcription factor that directly transactivates the ST2 promoter via Ets-family-related cis-element in mast cells and basophils.
authors: Atopy (Allergy) Research Center, Juntendo University School of Medicine, 2−1−1 Hongo, Bunkyo-ku, Tokyo, Japan.
authors: Yosuke
authors: Y
authors: Baba
authors: Keiko
authors: K
authors: Maeda
authors: Takuya
authors: T
authors: Yashiro
authors: Eisuke
authors: E
authors: Inage
authors: François
authors: F
authors: Niyonsaba
authors: Mutsuko
authors: M
authors: Hara
authors: Ryuyo
authors: R
authors: Suzuki
authors: Yoshikazu
authors: Y
authors: Ohtsuka
authors: Toshiaki
authors: T
authors: Shimizu
authors: Hideoki
authors: H
authors: Ogawa
authors: Ko
authors: K
authors: Okumura
authors: Chiharu
authors: C
authors: Nishiyama
mesh_terms: D001491:Basophils / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008407:Mast Cells / Q000378:metabolism*; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics*; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D000072179:Interleukin-1 Receptor-Like 1 Protein; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C079241:IL1RL1 protein, human