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Immunity. 1999 Dec;11(6):665-75.

Rapid and selective remodeling of a positioned nucleosome during the induction of IL-12 p40 transcription.

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Howard Hughes Medical Institute, Department of Microbiology, Immunology, and Molecular Genetics, University of California, 90095-1662, USA.


Nucleosomes are important for gene regulation, but comprehensive studies of nucleosome positioning, remodeling, and transcription factor binding at inducible mammalian promoters have not been reported. We have analyzed the IL-12 p40 promoter, which is induced in macrophages by bacterial products. High-resolution micrococcal nuclease analyses revealed that a positioned nucleosome, nucleosome 1, spans the promoter, with three positioned nucleosomes further upstream. Upon activation, nucleosome 1 was rapidly and selectively remodeled in a protein synthesis-dependent manner. In primary macrophages, IFNgamma synergistically enhanced p40 expression, but little effect on remodeling or promoter occupancy was observed. These results suggest that remodeling complexes are selectively targeted to a single, promoter-encompassing nucleosome and that IFNgamma influences an event that is independent or downstream of remodeling.

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