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Molecular and Cellular Biology, August 2005, p. 7386-7398, Vol. 25, No. 16
0270-7306/05/$08.00+0 doi:10.1128/MCB.25.16.7386-7398.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Cross Talk in Hormonally Regulated Gene Transcription through Induction of Estrogen Receptor Ubiquitylation
Min Luo,
Mingshi Koh,
Jiajun Feng,
Qiang Wu, and
Philippa Melamed*
Functional Genomics Laboratories, Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117542, Singapore
Received 7 May 2005/
Returned for modification 26 May 2005/
Accepted 31 May 2005
Estrogen tightly regulates the levels of circulating gonadotropins, but a direct effect of estrogen receptor alpha (ER
) on the mammalian LHß gene has remained poorly defined. We demonstrate here that ER
can associate with the LHß promoter through interactions with Sf-1 and Pitx1 without requiring an estrogen response element (ERE). We show that gonadotropin-releasing hormone (GnRH) promotes ER
ubiquitylation and also degradation while stimulating expression of ubc4. GnRH also increases the association and lengthens the cycling time of ER
on the LHß promoter. The ER
association and transactivation of the LHß gene, as well as ER
degradation, are increased following ubc4 overexpression, while the effects of GnRH are abated following ubc4 knockdown. Our results indicate that ER
ubiquitylation and subsequent transactivation of the LHß gene can be induced by increasing the levels of the E2 enzyme as a result of signaling by an extracellular hormone, thus providing a new form of cross talk in hormonally stimulated regulation of gene expression.
* Corresponding author. Mailing address: Functional Genomics Laboratories, Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117542, Singapore. Phone: (65) 68741882. Fax: (65) 68722013. E-mail: dbsmp{at}nus.edu.sg.
Authors contributed equally.
Molecular and Cellular Biology, August 2005, p. 7386-7398, Vol. 25, No. 16
0022-538X/05/$08.00+0 doi:10.1128/MCB.25.16.7386-7398.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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Copyright © 2005 by the American Society for Microbiology. All rights reserved.