title: STATs shape the active enhancer landscape of T cell populations.
abstract: Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. Although enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4(+) T cells as a model of differentiation, mapping the activity of cell-type-specific enhancer elements in T helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the activation of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells.
authors.affiliation: Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1930, USA.
authors.forename: Golnaz
authors.initials: G
authors.lastname: Vahedi
authors.forename: Hayato
authors.initials: H
authors.lastname: Takahashi
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakayamada
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Sun
authors.forename: Vittorio
authors.initials: V
authors.lastname: Sartorelli
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D050990:GATA3 Transcription Factor / Q000378:metabolism; D020043:Genes, Essential; D051379:Mice; D008810:Mice, Inbred C57BL; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology*; D018418:Th2 Cells / Q000166:cytology*; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D050791:STAT Transcription Factors; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D050880:p300-CBP Transcription Factors