T helper type 1-specific Brg1 recruitment and remodeling of nucleosomes positioned at the IFN-gamma promoter are Stat4 dependent.

Zhang F, Boothby M
J Exp Med. 2006 203 (6): 1493-505

PMID: 16717115 · PMCID: PMC2118309 · DOI:10.1084/jem.20060066

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.

MeSH Terms (16)

Animals CD4-Positive T-Lymphocytes Cell Nucleus Chromatin DNA Helicases Interferon-gamma Mice Mice, Inbred BALB C Nuclear Proteins Nucleosomes Polymerase Chain Reaction Promoter Regions, Genetic STAT4 Transcription Factor T-Lymphocytes Th1 Cells Transcription Factors

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