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1 September 2004 Ontogeny of a Demethylation Domain and Its Relationship to Activation of Tissue-Specific Transcription
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Abstract

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.

Christopher B. Geyer, Christine Mione Kiefer, Thomas P. Yang, and John R. McCarrey "Ontogeny of a Demethylation Domain and Its Relationship to Activation of Tissue-Specific Transcription," Biology of Reproduction 71(3), 837-844, (1 September 2004). https://doi.org/10.1095/biolreprod.104.028969
Received: 27 February 2004; Accepted: 1 May 2004; Published: 1 September 2004
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