p33 ING1b and estrogen receptor (ER)α

The ING1 gene was originally cloned as a candidate tumor suppressor of human breast cancer astr and recent studies suggest that ING1 proteins are involved in chromatin remodeling functions via physical association with both histone acetyltransferases (HATs) and histone deacetylases (HDACs). Both CREB binding protein (CBP) and the related p300 proteins show a marked preference for binding to complexes containing p33 INGIb, one of the major ING1 isoforms, whereas HDAC immunocomplexes contain equal amounts of p33 INGIband p47 INGIb This observation is interesting, given that p33 INGIbcan selectively increase histone H3 and H4 acetylation when micro-injected into individual cells, whereas p47 INGIb inhibits histone acetylation. We investigated whether p33 INGIb modulated the transcriptional activity of estrogen receptor (ER) α. In cells transfected with increasing concentrations of a mammalian expression vector encoding p33 INGIb estrogen-induced ERα transcriptional activity was found to increase in a dose-dependent manner. As p33 INGIb expression levels increased, transcription of an ER-responsive reporter gene by either estrogen-inducible full-length ERa or the activation function (AF) 1 deletion mutant was enhanced, while the AF2 deletion mutant was unaffected by the presence of p33 INGIb These results showed that p33 INGIb enhanced estrogen-induced ERa activity through the AF2 domain. Our data demonstrate that p33 INGIbacts like a coactivator for ERα and stimulates estrogen-induced ER α transcriptional activity consistent with a function for p33 INGIb in chromatin remodeling.