T helper type 1-specific Brg1 recruitment and remodeling of nucleosomes positioned at the IFN-gamma promoter are Stat4 dependent.
Transcriptional competence of the interferon-gamma (IFN-gamma) locus is enhanced as Th1 effectors develop from naive CD4 T lymphocytes; conversely, this gene is repressed during Th2 differentiation. We now show that the Switch (Swi)-sucrose nonfermenter (SNF) component Brahma-related gene 1 (Brg1) is recruited, and positioned nucleosomes are remodeled, in a Th1-specific manner that is dependent on the transcription factor Stat4 and calcineurin phosphatase activity. Interference with specific components of mammalian Swi-SNF complexes decreased CD4 T cell differentiation into IFN-gamma-positive Th1 cells. These findings reveal a collaborative mechanism of IFN-gamma gene regulation during Th1 differentiation and suggest that a Th1-specific chromatin structure is created by early recruitment of Swi-SNF complexes and nucleosome remodeling dependent on Stat4 and calcineurin activation.
Zhang
Fuping
F
Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Boothby
Mark
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002467:Cell Nucleus / Q000502:physiology; D002843:Chromatin / Q000502:physiology; D004265:DNA Helicases; D007371:Interferon-gamma / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins / Q000502:physiology*; D009707:Nucleosomes / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D050797:STAT4 Transcription Factor / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000502:physiology*
D002843:Chromatin; D009687:Nuclear Proteins; D009707:Nucleosomes; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D014157:Transcription Factors; D007371:Interferon-gamma; C513194:Smarca4 protein, mouse; D004265:DNA Helicases