Ontogeny of a demethylation domain and its relationship to activation of tissue-specific transcription.
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.
Geyer
Christopher B
CB
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
Kiefer
Christine Mione
CM
Yang
Thomas P
TP
McCarrey
John R
JR
D000818:Animals; D018899:CpG Islands / Q000502:physiology; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010735:Phosphoglycerate Kinase / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis / Q000196:embryology* / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology; D019076:Transgenes / Q000502:physiology
D007527:Isoenzymes; D010735:Phosphoglycerate Kinase; C104317:phosphoglycerate kinase, testis specific