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Biology of Reproduction 59, 284-292 (1998)
©Copyright 1998 Society for the Study of Reproduction, Inc.

A Gene-Specific Promoter in Transgenic Mice Directs Testis-Specific Demethylation Prior to Transcriptional Activation In Vivo1

L. Peter Zhangc,d, James C. Stroudc, Christi A. Walterd, Gwendolyn S. Adriand, , and John R. McCarrey2,c,d

c Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78245 d Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284

Transcription of the autosomal phosphoglycerate kinase gene, Pgk-2, is initiated at the onset of meiosis during spermatogenesis in mammals. However, in the mouse, the 5' portion of the endogenous Pgk-2 coding sequence undergoes a specific demethylation event that precedes transcriptional activation by 10–12 days. Here we show that transgenes consisting of the Pgk-2 core promoter ligated to the CAT reporter gene undergo a similar tissue-, stage-, and cell type-specific demethylation in the 5' portion of the CAT coding sequence, whereas transgenes consisting of the CAT reporter sequence alone, or of the CAT sequence ligated to the CpG island-containing transferrin gene promoter, demonstrate different patterns of demethylation. These results indicate that specific promoter sequences can influence the pattern of tissue-specific demethylation within different genes and that a signal for spermatogenic cell-specific demethylation resides within the core promoter of the mammalian Pgk-2 gene.

1 This work was supported by grants from the NIH (HD 23126 to J.R.M. and CA 61335 to C.A.W.).

2 Correspondence: John R. McCarrey, Department of Genetics, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, TX 78245. FAX: (210) 670–3316; johnmc{at}darwin.sfbr.org




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