title: YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity.
abstract: Regulatory T (T(reg)) cells are essential for maintenance of immune homeostasis. Foxp3 is the key transcription factor for T(reg)-cell differentiation and function; however, molecular mechanisms for its negative regulation are poorly understood. Here we show that YY1 expression is lower in T(reg) cells than T(conv) cells, and its overexpression causes a marked reduction of Foxp3 expression and abrogation of suppressive function of Treg cells. YY1 is increased in T(reg) cells under inflammatory conditions with concomitant decrease of suppressor activity in dextran sulfate-induced colitis model. YY1 inhibits Smad3/4 binding to and chromatin remodelling of the Foxp3 locus. In addition, YY1 interrupts Foxp3-dependent target gene expression by physically interacting with Foxp3 and by directly binding to the Foxp3 target genes. Thus, YY1 inhibits differentiation and function of T(reg) cells by blocking Foxp3.
authors.affiliation: Department of Life Science, Sogang University, 35 Baekbeom-ro, Seoul 121-742, Korea.|Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.|Howard Hughes Medical Institute, Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Soo Seok
authors.initials: SS
authors.lastname: Hwang
authors.affiliation: Department of Life Science, Sogang University, 35 Baekbeom-ro, Seoul 121-742, Korea.
authors.forename: Sung Woong
authors.initials: SW
authors.lastname: Jang
authors.affiliation: Department of Life Science, Sogang University, 35 Baekbeom-ro, Seoul 121-742, Korea.
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.|Howard Hughes Medical Institute, Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Lark Kyun
authors.initials: LK
authors.lastname: Kim
authors.affiliation: Department of Rheumatology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.|Department of Plastic and Reconstructive Surgery, Hand Surgery-Burn Center, Medical Faculty, RWTH Aachen University, Templergraben 55, 52062 Aachen, Germany.|Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Templergraben 55, 52062 Aachen, Germany.
authors.forename: Bong-Sung
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Life Science, Sogang University, 35 Baekbeom-ro, Seoul 121-742, Korea.
authors.forename: Hyeong Su
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Life Science, Sogang University, 35 Baekbeom-ro, Seoul 121-742, Korea.
authors.forename: Kiwan
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Life Science, Sogang University, 35 Baekbeom-ro, Seoul 121-742, Korea.
authors.forename: Wonyong
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.|Howard Hughes Medical Institute, Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.affiliation: Department of Life Science, Sogang University, 35 Baekbeom-ro, Seoul 121-742, Korea.
authors.forename: Gap Ryol
authors.initials: GR
authors.lastname: Lee
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003092:Colitis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse