Ontogeny of a demethylation domain and its relationship to activation of tissue-specific transcription

Christopher B. Geyer, Christine Mione Kiefer, Thomas P. Yang, John R. McCarrey

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)837-844
Number of pages8
JournalBiology of reproduction
Volume71
Issue number3
DOIs
StatePublished - Sep 2004

Keywords

  • Gametogenesis
  • Gene regulation
  • Spermatogenesis
  • Testis

ASJC Scopus subject areas

  • Cell Biology

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