title: Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation.
abstract: Signal transducer and activator of transcription 4 (STAT4) and STAT6 are key factors in the specification of helper T cells; however, their direct roles in driving differentiation are not well understood. Using chromatin immunoprecipitation and massive parallel sequencing, we quantitated the full complement of STAT-bound genes, concurrently assessing global STAT-dependent epigenetic modifications and gene transcription by using cells from cognate STAT-deficient mice. STAT4 and STAT6 each bound over 4000 genes with distinct binding motifs. Both played critical roles in maintaining chromatin configuration and transcription of a core subset of genes through the combination of different epigenetic patterns. Globally, STAT4 had a more dominant role in promoting active epigenetic marks, whereas STAT6 had a more prominent role in antagonizing repressive marks. Clusters of genes negatively regulated by STATs were also identified, highlighting previously unappreciated repressive roles of STATs. Therefore, STAT4 and STAT6 play wide regulatory roles in T helper cell specification.
authors.affiliation: Molecular Immunology and Inflammation Branch, NIAMS, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Golnaz
authors.initials: G
authors.lastname: Vahedi
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Sun
authors.forename: Wendy T
authors.initials: WT
authors.lastname: Watford
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takatori
authors.forename: Haydee L
authors.initials: HL
authors.lastname: Ramos
authors.forename: Hayato
authors.initials: H
authors.lastname: Takahashi
authors.forename: Jonathan
authors.initials: J
authors.lastname: Liang
authors.forename: Gustavo
authors.initials: G
authors.lastname: Gutierrez-Cruz
authors.forename: Chongzhi
authors.initials: C
authors.lastname: Zang
authors.forename: Weiqun
authors.initials: W
authors.lastname: Peng
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000276:immunology*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor