title: Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells.
abstract: The transcription factor Foxp3 is indispensable for the ability of regulatory T cells (Treg cells) to suppress fatal inflammation. Here we characterized the role of Foxp3 in chromatin remodeling and the regulation of gene expression in actively suppressive Treg cells in an inflammatory setting. Although genome-wide occupancy of regulatory elements in DNA by Foxp3 was similar in resting Treg cells and those activated in vivo, Foxp3-bound enhancer elements in the DNA were poised for repression only in activated Treg cells. Following activation, Foxp3-bound sites showed diminished accessibility of chromatin and selective deposition of histone H3 trimethylated at Lys27 (H3K27me3), which was associated with recruitment of the histone methyltransferase Ezh2 and downregulation of the expression of nearby genes. Thus, Foxp3 poises its targets for repression by facilitating the formation of repressive chromatin in Treg cells upon their activation in response to inflammatory cues.
authors.affiliation: Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.|Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Arvey
authors.affiliation: Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.|Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Joris
authors.initials: J
authors.lastname: van der Veeken
authors.affiliation: Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.|Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Samstein
authors.affiliation: Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.|Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Genome Sciences, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Stamatoyannopoulos
authors.affiliation: Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.|Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.|Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Rudensky
mesh_terms: D000818:Animals; D002843:Chromatin / Q000276:immunology; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation; D000071221:Enhancer of Zeste Homolog 2 Protein; D051858:Forkhead Transcription Factors / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006657:Histones / Q000235:genetics; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006657:Histones; D011948:Receptors, Antigen, T-Cell; D004247:DNA; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2
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