The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published online 22 May 2006 doi:10.1084/jem.20060066
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 6, 1493-1505
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ARTICLE

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

Fuping Zhang1 and Mark Boothby1,2

1 Department of Microbiology and Immunology and 2 Rheumatology Division, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232

CORRESPONDENCE Mark Boothby: mark.boothby{at}vanderbilt.edu

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.

Abbreviations used: BAF, Brg1-associated factor; Brg1, Brahma-related gene 1; ChIP, chromatin IP; CsA, cyclosporin A; IP, immunoprecipitation; LM-PCR, ligation-mediated PCR; MNase, micrococcal nuclease; RE, restriction enzyme; REA, RE accessibility; RNAi, RNA interference; SNF, sucrose nonfermenter; Swi, Switch.


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