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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,{dagger} Mingshi Koh,{dagger} 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{alpha}) on the mammalian LHß gene has remained poorly defined. We demonstrate here that ER{alpha} 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{alpha} ubiquitylation and also degradation while stimulating expression of ubc4. GnRH also increases the association and lengthens the cycling time of ER{alpha} on the LHß promoter. The ER{alpha} association and transactivation of the LHß gene, as well as ER{alpha} degradation, are increased following ubc4 overexpression, while the effects of GnRH are abated following ubc4 knockdown. Our results indicate that ER{alpha} 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.

{dagger} 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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