BOR - Papers in Press, published online ahead of print
May 12, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.028969
BIOLOGY OF REPRODUCTION 71, 837844 (2004)
DOI: 10.1095/biolreprod.104.028969
© 2004 by the Society for the Study of Reproduction, Inc.
Ontogeny of a Demethylation Domain and Its Relationship to Activation of Tissue-Specific Transcription1
Christopher B. Geyer3,
Christine Mione Kiefer4,
Thomas P. Yang4,6, and
John R. McCarrey2,3,7
Department of Cellular and Structural Biology,3 University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229
Department of Biochemistry and Molecular Biology,4
Center for Mammalian Genetics,5
Department of Pediatrics,6 University of Florida School of Medicine, Gainesville, Florida 32611
Department of Biology,7 University of Texas at San Antonio, San Antonio, Texas 78249
We examined DNA methylation throughout the endogenous murine testis-specific phosphoglycerate kinase (Pgk2) gene and in human PGK2 promoter/CAT reporter transgenes in mouse spermatogenic cells before, during, and following the period of active transcription of this gene. We observed the gradual development of a domain of demethylation beginning over the promoter and then expanding approximately 1 kilobase in each direction within the endogenous Pgk2 gene. This demethylation domain develops in the absence of DNA replication and precedes other molecular changes that potentiate tissue-specific activation of this gene. Studies with transgenes show that a signal residing in the Pgk2 core promoter directs this gene-, cell type-, and stage-specific demethylation process. These results are consistent with a model in which regulated, tissue- and gene-specific demethylation initiates a cascade of subsequent molecular events required for tissue-specific activation of transcription during spermatogenesis in vivo.
1 Supported by a grant from the NIH to J.R.M. (HD 40891).
2 Correspondence. FAX: 210.458.5658; jmccarrey{at}utsa.edu
Copyright © 2004 by the Society for the Study of Reproduction.