An inactivating mutation of th

With the example of CITED1, aCBP/p300-binding nuclear protein that does not bind directly toDNA, is a transcriptional coregulator.

Here, evidence that CITED1 functionsas a selective coactivator for estrogen-dependenttranscription.

When transfected, CITED1 enhancedtranscriptional activation by the ligand-binding/AF2 domain of bothestrogen receptor-? (ER?) and ER? in an estrogen-dependent manner,but it affected transcriptional activities of other nuclearreceptors only marginally.

CITED1 bound directly to ER? in anestrogen-dependent manner through its transactivating domain, andthis binding activity was separable from its p300-bindingactivity.

CITED1 was strongly expressed innulliparous mouse mammary epithelial cells and, when expressed inER-positive MCF-7 breast cancer cells by transduction, exogenousCITED1 enhanced sensitivity of MCF-7 cells to estrogen, stabilizingthe estrogen-dependent interaction between p300 and ER?.

The estrogen-induced expression ofthe transforming growth factor-? (TGF-?) mRNA transcript wasenhanced in the CITED1-expressing MCF-7 cells, whereasestrogen-induced expression of the mRNA transcripts forprogesterone receptor or pS2 was not affected.

Chromatin immunoprecipitation assayrevealed that endogenous CITED1 is recruited to the chromosomalTGF-? promoter in MCF-7 cells in an estrogen-dependentmanner but not to the pS2 promoter.

These results suggest that CITED1may play roles in regulation of estrogen sensitivity in agene-specific manner.