title: Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation.
abstract: The Th2 locus control region (LCR) has been shown to be important in efficient and coordinated cytokine gene regulation during Th2 cell differentiation. However, the molecular mechanism for this is poorly understood. To study the molecular mechanism of the Th2 LCR, we searched for proteins binding to it. We discovered that transcription factor YY1 bound to the LCR and the entire Th2 cytokine locus in a Th2-specific manner. Retroviral overexpression of YY1 induced Th2 cytokine expression. CD4-specific knockdown of YY1 in mice caused marked reduction in Th2 cytokine expression, repressed chromatin remodeling, decreased intrachromosomal interactions, and resistance in an animal model of asthma. YY1 physically associated with GATA-binding protein-3 (GATA3) and is required for GATA3 binding to the locus. YY1 bound to the regulatory elements in the locus before GATA3 binding. Thus, YY1 cooperates with GATA3 and is required for regulation of the Th2 cytokine locus and Th2 cell differentiation.
authors.affiliation: Department of Life Science,  Sogang University, Seoul,  Korea 121-742.
authors.forename: Soo Seok
authors.initials: SS
authors.lastname: Hwang
authors.forename: Young Uk
authors.initials: YU
authors.lastname: Kim
authors.forename: Sumin
authors.initials: S
authors.lastname: Lee
authors.forename: Sung Woong
authors.initials: SW
authors.lastname: Jang
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Byung Hee
authors.initials: BH
authors.lastname: Koh
authors.forename: Wonyong
authors.initials: W
authors.lastname: Lee
authors.forename: Joomyeong
authors.initials: J
authors.lastname: Kim
authors.forename: Abdallah
authors.initials: A
authors.lastname: Souabni
authors.forename: Meinrad
authors.initials: M
authors.lastname: Busslinger
authors.forename: Gap Ryol
authors.initials: GR
authors.lastname: Lee
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D042002:Chromatin Assembly and Disassembly / Q000276:immunology; D047369:Chromatin Immunoprecipitation; D016207:Cytokines; D024202:Electrophoretic Mobility Shift Assay; D005455:Fluorescent Antibody Technique; D050990:GATA3 Transcription Factor / Q000378:metabolism; D015151:Immunoblotting; D047468:Immunoprecipitation; D019901:Locus Control Region / Q000235:genetics / Q000276:immunology; D008156:Luciferases; D051379:Mice; D008822:Mice, Transgenic; D009841:Oligonucleotides / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology*; D050986:YY1 Transcription Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D009841:Oligonucleotides; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; D008156:Luciferases