Article

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

Department of Physiology, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, MA 01655-0127. USA.
Molecular and Cellular Biology (Impact Factor: 5.04). 01/2005; 24(24):10681-8. DOI: 10.1128/MCB.24.24.10681-10688.2004
Source: PubMed

ABSTRACT 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.

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    • "Four members of the SREBP family, SREBP-1a, SREBP-1c, SREBP-2 and SREBP-2gc, have been identified [2-5]. SREBPs are a family of transcription factors that have independently been characterized as mediators of cellular cholesterol homeostasis [6,7] and as regulators of fatty acid biosynthesis and uptake [8-10]. "
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    • "In testing the system, we noted the presence of the YY1 response element in the upstream regions of all three genes in the protamine domain that has been associated with a sterol response element binding protein that regulates proacrosin, another haploid expressed gene. [39]. The developmentally significant GATA family of elements were also over-represented in biologically significant locations in two of the three genes. "
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    • "The post-meiotic transcription of genes raises the possibility of the specific expression of X or Y chromosomal genes localised in round spermatids and cytoplasmic fragments (Hendrikson et al. 1995). Among the candidate genes that have been implicated in testicular post-meiotic germ cell development are Xist, CREMtau, p63, SREBP2 gc and extra-embryonic tissue-spermatogenesis-homeobox gene 1 (Esx1, also known as Spx1; Dolci et al. 1994; Poulat et al. 1995; Li et al. 1997; Li and Behringer 1998; Nakamuta and Kobayashi 2004; Wang et al. 2004). To examine the possibility of these gene products being used as markers for X chromosome-bearing sperm, we investigated Esx1. "
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