This Article Full Text Full Text (PDF) All Versions of this Article: 147/1/324    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yaden, B. C. Articles by Rhodes, S. J. Search for Related Content PubMed PubMed Citation Articles by Yaden, B. C. Articles by Rhodes, S. J.

Two Promoters Mediate Transcription from the Human LHX3 Gene: Involvement of Nuclear Factor I and Specificity Protein 1

Department of Cellular and Integrative Physiology (S.J.R.), Indiana University School of Medicine, Indianapolis, Indiana 46202; Department of Biology (B.C.Y., M.G.), Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202; and U.S. Department of Agriculture/Agricultural Research Service (T.P.L.S.), U.S. Meat Animal Research Center, Clay Center, Nebraska 68933

Address all correspondence and requests for reprints to: Simon J. Rhodes, Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Medical Science Building Room 362A, 635 North Barnhill Drive, Indianapolis, Indiana 46202. E-mail: srhodes{at}iupui.edu.

The LHX3 transcription factor is required for pituitary and nervous system development in mammals. Mutations in the human gene are associated with hormone-deficiency diseases. The gene generates two mRNAs, hLHX3a and hLHX3b, which encode three proteins with different properties. Here, the cis elements and trans-acting factors that regulate the basal transcription of the two mRNAs are characterized. A comparative approach was taken featuring analysis of seven mammalian Lhx3 genes, with a focus on the human gene. Two conserved, TATA-less, GC-rich promoters that are used to transcribe the mRNAs precede exons 1a and 1b of hLHX3. Transcription start sites were mapped for both promoters. Deletion experiments showed most activity for reporter genes containing the basal promoters in the context of –2.0 kb of hLHX3a and 1.8 kb of intron 1a (hLHX3b). Transfection, site-directed mutation, electrophoretic mobility shift, Southwestern blot, and chromatin immunoprecipitation approaches were used to characterize the interaction of transcription factors with conserved elements in the promoters. Specificity protein 1 is a regulator of both promoters through interaction with GC boxes. In addition, a distal element within intron 1a that is recognized by nuclear factor I is critical for hLHX3b promoter function. We conclude that dual promoters allow regulated production of two hLHX3 mRNAs.

This article has been cited by other articles:

				A. Rajab, D. Kelberman, S. C.P. de Castro, H. Biebermann, H. Shaikh, K. Pearce, C. M. Hall, G. Shaikh, D. Gerrelli, A. Grueters, et al. Novel mutations in LHX3 are associated with hypopituitarism and sensorineural hearing loss Hum. Mol. Genet., July 15, 2008; 17(14): 2150 - 2159. [Abstract] [Full Text] [PDF]