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Molecular and Cellular Biology, December 2004, p. 10681-10688, Vol. 24, No. 24
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.24.10681-10688.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Novel Role for a Sterol Response Element Binding Protein in Directing Spermatogenic Cell-Specific Gene Expression

Hang Wang,1 Jovenal T. San Agustin,2 George B. Witman,2 and Daniel L. Kilpatrick1*

Department of Physiology,1 Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts2

Received 1 July 2004/ Returned for modification 1 August 2004/ Accepted 26 September 2004

Sperm are highly specialized cells, and their formation requires the synthesis of a large number of unique mRNAs. However, little is known about the transcriptional mechanisms that direct male germ cell differentiation. Sterol response element binding protein 2gc (SREBP2gc) is a spermatogenic cell-enriched isoform of the ubiquitous transcription factor SREBP2, which in somatic cells is required for homeostatic regulation of cholesterol. SREBP2gc is selectively enriched in spermatocytes and spermatids, and, due to its novel structure, its synthesis is not subject to cholesterol feedback control. This suggested that SREBP2gc has unique cell- and stage-specific functions during spermatogenesis. Here, we demonstrate that this factor activates the promoter for the spermatogenesis-related gene proacrosin in a cell-specific manner. Multiple SREBP2gc response elements were identified within the 5'-flanking and proximal promoter regions of the proacrosin promoter. Mutating these elements greatly diminished in vivo expression of this promoter in spermatogenic cells of transgenic mice. These studies define a totally new function for an SREBP as a transactivator of male germ cell-specific gene expression. We propose that SREBP2gc is part of a cadre of spermatogenic cell-enriched isoforms of ubiquitously expressed transcriptional coregulators that were specifically adapted in concert to direct differentiation of the male germ cell lineage.

* Corresponding author. Mailing address: Department of Physiology, University of Massachusetts Medical School, 55 Lake Ave. N, Worcester, MA 01655-0127. Phone: (508) 856-6274. Fax: (508) 856-5997. E-mail: Daniel.Kilpatrick{at}Umassmed.edu.

Molecular and Cellular Biology, December 2004, p. 10681-10688, Vol. 24, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.24.10681-10688.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Heemers, H. V., Verhoeven, G., Swinnen, J. V. (2006). Androgen Activation of the Sterol Regulatory Element-Binding Protein Pathway: Current Insights. Mol. Endocrinol. 20: 2265-2277 [Abstract] [Full Text]  
  • Wang, H., Sartini, B. L., Millette, C. F., Kilpatrick, D. L. (2006). A Developmental Switch in Transcription Factor Isoforms During Spermatogenesis Controlled by Alternative Messenger RNA 3'-End Formation. Biol. Reprod. 75: 318-323 [Abstract] [Full Text]  


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