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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2005-9-27
pubmed:abstractText
Cardiovascular tissues are important targets of estrogen action. Vascular cells express the two known estrogen receptors (ERs), ERalpha and ERbeta, ligand-activated transcription factors that regulate gene transcription through interactions with both coactivator and corepressor molecules. To isolate ERalpha coregulators in vascular cells, we performed a yeast two-hybrid screen for ERalpha-interacting proteins using a human aorta library. Here we report the identification of modulator recognition factor 1 (MRF1) as an ERalpha-interacting corepressor protein. Full-length MRF1 binds to both the N terminus and the C terminus of ERalpha. ERalpha and MRF1 coimmunoprecipitate in an estradiol-independent manner, and recombinant ERalpha binds to both full-length and COOH-terminal MRF1 in the absence of estradiol. MRF1 also interacts in a ligand-dependent manner with thyroid receptor alpha, retinoid X receptor alpha, and androgen receptor, and in a ligand-independent manner with ERbeta and the retinoic acid receptor. MRF1 RNA is highly expressed in aorta, heart, skeletal muscle, and liver. MRF1 has intrinsic repressor activity in an in vitro GAL reporter assay. Transient transfection studies show that MRF1 represses transcription by ERalpha activated by estradiol in a dose-dependent manner, as well as by the selective ER modulators 4-hydroxy-tamoxifen and raloxifene. MRF1 repression is not influenced by pharmacological inhibition of histone deacetylase. These data identify MRF1 as a repressor of ERalpha-mediated transcriptional activation and support a role for MRF1 in regulating ER-dependent gene expression in cardiovascular and other cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2491-501
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Modulator recognition factor 1, an AT-rich interaction domain family member, is a novel corepressor for estrogen receptor alpha.
pubmed:affiliation
Molecular Cardiology Research Institute, New England Medical Center and Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111,USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural