CBP recruitment and histone acetylation in differential gene induction by glucocorticoids and progestins

Abstract

We have analyzed histone acetylation at the steroid-responsive mouse mammary tumor virus (MMTV) promoter in five separate cell lines that express functional glucocorticoid and/or progesterone receptors. Chromatin immunoprecipitation assays reveal that glucocorticoid and progesterone receptors bind the MMTV promoter after hormone addition but that receptor binding is not associated with an increase in acetylation of histone H3 or H4. We have, however, found one exception to this rule. Previously we described a cell line [T47D(C&L)] that displayed a remarkable differential induction of MMTV by glucocorticoids and progestins. At one chromosomal locus (MMTV-luciferase), MMTV is preferentially induced by glucocorticoids, whereas at another locus within the same cell (MMTV-CAT), MMTV is activated by both glucocorticoids and progestins. Here we show that the glucocorticoid-mediated induction of MMTV-luciferase is accompanied by increased recruitment of CBP to the promoter and increased histone H3 and H4 acetylation, whereas the hormonal induction of MMTV-CAT in the same cell exhibits a more modest CBP recruitment without any increase in histone acetylation. These studies suggest that increased histone acetylation may serve a potentiating function for MMTV promoter activation at certain loci. However, increased histone acetylation is not requisite for steroid-mediated induction of transcription at all genes.