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 DNA, is a transcriptional coregulator. Here, we show evidence that CITED1 functions as a selective coactivator for estrogen-dependent transcription. When transfected, CITED1 enhanced transcriptional activation by the ligand-binding/AF2 domain of both estrogen receptor-alpha (ERalpha) and ERbeta in an estrogen-dependent manner, but it affected transcriptional activities of other nuclear receptors only marginally. CITED1 bound directly to ERalpha in an estrogen-dependent manner through its transactivating domain, and this binding activity was separable from its p300-binding activity. CITED1 was strongly expressed in nulliparous mouse mammary epithelial cells and, when expressed in ER-positive MCF-7 breast cancer cells by transduction, exogenous CITED1 enhanced sensitivity of MCF-7 cells to estrogen, stabilizing the estrogen-dependent interaction between p300 and ERalpha. The estrogen-induced expression of the transforming growth factor-alpha (TGF-alpha) mRNA transcript was enhanced in the CITED1-expressing MCF-7 cells, whereas estrogen-induced expression of the mRNA transcripts for progesterone receptor or pS2 was not affected. Chromatin immunoprecipitation assay revealed that endogenous 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 results suggest that CITED1 may play roles in regulation of estrogen sensitivity in a gene-specific manner.
Yahata
T
T
Laboratory of Tumor Biology, Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
Shao
W
W
Endoh
H
H
Hur
J
J
Coser
K R
KR
Sun
H
H
Ueda
Y
Y
Kato
S
S
Isselbacher
K J
KJ
Brown
M
M
Shioda
T
T
D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D017931:DNA Primers; D050881:E1A-Associated p300 Protein; D004967:Estrogens / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D016211:Transforming Growth Factor alpha / Q000235:genetics; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004967:Estrogens; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D016211:Transforming Growth Factor alpha; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse