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

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