TAILIEUCHUNG - Báo cáo khoa học: Involvement of NF-jB subunit p65 and retinoic acid receptors, RARa and RXRa, in transcriptional regulation of the human GnRH II gene

Gonadotropin-releasing hormone (GnRH) I and II are hypothalamic deca-peptides with pivotal roles in the development of reproductive competence and regulation of reproductive events. In this study, transcriptional regula-tion of the human GnRH IIgene was investigated. | ỊFEBS Journal Involvement of NF-kB subunit p65 and retinoic acid receptors RARa and RXRa in transcriptional regulation of the human GnRH II gene Ruby L. C. Hoo1 Kathy Y. Y. Chan2 Francis K. Y. Leung1 Leo T. O. Lee1 Peter C. K. Leung3 and Billy K. C. Chow3 1 Schoolof BiologicalSciences University of Hong Kong Pokfulam Road Hong Kong China 2 Department of Paediatrics Chinese University of Hong Kong Prince of Wales Hospital Shatin Hong Kong China 3 Department of Obstetrics and Gynecology University of British Columbia Vancouver Canada Keywords gonadotropin-releasing hormone II NF-kB subunit p65 retinoic acid receptors silencer transcriptional regulation Correspondence B. K. C. Chow Schoolof Biological Sciences University of Hong Kong Pokfulam Road Hong Kong China Tel 852 2299 0850 Fax 852 2857 4672 E-mail bkcc@ Present address Department of Medicine Li Ka Shing Faculty of Medicine University of Hong Kong Queen Mary Hospital Hong Kong Received 1 November 2006 revised 19 March 2007 accepted 22 March 2007 doi Gonadotropin-releasing hormone GnRH I and II are hypothalamic decapeptides with pivotal roles in the development of reproductive competence and regulation of reproductive events. In this study transcriptional regulation of the human GnRH II gene was investigated. By scanning mutation analysis coupled with transient promoter assays the motif at -641 -636 CATGCC designated GII-Sil was identified as a repressor element. Mutation of this motif led to full restoration of promoter activity in TE671 medulloblastoma and JEG-3 placenta choriocarcinoma cells. Supershift and chromatin immunoprecipitation assays showed in vitro and in vivo binding of NF-kB subunit p65 and the retinoic acid receptors RARa and RXRa to the promoter sequences. Over-expression of these protein factors indicated that p65 is a potent repressor and the RARa RXRa heterodimer is involved in the differential regulation of the GnRH II gene in neuronal and .

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