title: RHS6 coordinately regulates the Th2 cytokine genes by recruiting GATA3, SATB1, and IRF4.
abstract: BACKGROUND
  Asthma is a Th2 cell-driven inflammatory disease and a major public health concern. The cis-acting element Rad50 hypersensitive site 6 (RHS6) in the Th2 locus control region is essential for regulation of the Th2 cytokine genes; however, its role in allergic airway inflammation and underlying molecular mechanisms of the regulation by RHS6 are poorly understood.
  
  
  OBJECTIVE
  We sought to understand the role of RHS6 in the development of allergic airway inflammation and its molecular mechanism for Th2 cytokine expression.
  
  
  METHODS
  We used an ovalbumin-induced allergic inflammation model with RHS6-deficient mice to examine the role of RHS6 in this process. To examine molecular mechanism of RHS6 for Th2 cytokine expression, we used DNA affinity chromatography and mass spectrometry, quantitative RT-PCR, ELISA, intracellular cytokine staining, chromatin immunoprecipitation, and co-immunoprecipitation.
  
  
  RESULTS
  Deletion of RHS6 caused a dramatic resistance to allergic airway inflammation. RHS6 recruited transcription factors GATA3, SATB1, and IRF4, which play important roles in expression of all three Th2 cytokine genes. RHS6 deficiency caused inhibition of transcription factor-induced Th2 cytokine gene expression.
  
  
  CONCLUSIONS
  RHS6 is a critical regulatory element for allergic airway inflammation and for coordinate regulation of Th2 cytokine genes by recruiting GATA3, SATB1, and IRF4.
authors.affiliation: Department of Life Science, Sogang University, Mapo-gu, Seoul, Korea.
authors.forename: S S
authors.initials: SS
authors.lastname: Hwang
authors.affiliation: Department of Life Science, Sogang University, Mapo-gu, Seoul, Korea.
authors.forename: S W
authors.initials: SW
authors.lastname: Jang
authors.affiliation: Department of Life Science, Sogang University, Mapo-gu, Seoul, Korea.
authors.forename: K O
authors.initials: KO
authors.lastname: Lee
authors.affiliation: Department of Life Science, Sogang University, Mapo-gu, Seoul, Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Life Science, Sogang University, Mapo-gu, Seoul, Korea.
authors.forename: G R
authors.identifier: http://orcid.org/0000-0002-6412-9482
authors.initials: GR
authors.lastname: Lee
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D017766:Acid Anhydride Hydrolases; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D056426:Genetic Loci; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D019901:Locus Control Region; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D000099218:Interferon Regulatory Factor-4
chemical_list: D018528:ATP-Binding Cassette Transporters; D017766:Acid Anhydride Hydrolases; D016207:Cytokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; D050835:Interferon Regulatory Factors; D036961:Matrix Attachment Region Binding Proteins; D000099218:Interferon Regulatory Factor-4; C469541:Satb1 protein, mouse; C495198:Rad50 protein, mouse
keywords: RHS6; Th2 cytokine; asthma; cis-element; transcription factor