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Rapid and Selective Remodeling of a Positioned Nucleosome during the Induction of IL-12 p40 Transcription

by: Amy S Weinmann, Scott E Plevy, Stephen T Smale
Immunity, Vol. 11, No. 6. (1 December 1999), pp. 665-675.


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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, IFN[gamma] 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 IFN[gamma] influences an event that is independent or downstream of remodeling.


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