Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300-binding protein

CITED1, a CBP/p300.binding nuclear protein that does not bind directly to D NA, is a transcriptional coregulator. Here, we show evidence that CITED1 fu nctions as a selective coactivator for estrogen-dependent transcription. Wh en transfected, CITED1 enhanced transcriptional activation by the ligand-bi nding/AF2 domain of both estrogen receptor-alpha (ER alpha) and ER beta in an estrogen-dependent manner, but it affected transcriptional activities of other nuclear receptors only marginally. CITED1 bound directly to ER alpha in an estrogen-dependent manner through its transactivating domain, and th is binding activity was separable from its p300-binding activity. CITED1 wa s strongly expressed in nulliparous mouse mammary epithelial cells and, whe n expressed in ER-positive MCF-7 breast cancer cells by transduction, exoge nous CITED1 enhanced sensitivity of MCF-7 cells to estrogen, stabilizing th e estrogen-dependent interaction between p300 and ER alpha. The estrogen-in duced expression of the transforming growth factor-alpha (TGF-alpha) mRNA t ranscript was enhanced in the CITED1-expressing MCF-7 cells, whereas estrog en-induced expression of the mRNA transcripts for progesterone receptor or pS2 was not affected. Chromatin immunoprecipitation assay revealed that end ogenous CITED1 is recruited to the chromosomal TGF-alpha promoter in MCF-7 cells in an estrogen-dependent manner but not to the pS2 promoter. These re sults suggest that CITED1 may play roles in regulation of estrogen sensitiv ity in a gene-specific manner.