Vezf1 regulates genomic DNA methylation through its effects on expression of DNA methyltransferase Dnmt3b.
The zinc finger protein vascular endothelial zinc finger 1 (Vezf1) has been implicated in the development of the blood vascular and lymphatic system in mice, and has been characterized as a transcriptional activator in some systems. The chicken homolog, BGP1, has binding sites in the beta-globin locus, including the upstream insulator element. We report that in a mouse embryonic stem cell line deletion of both copies of Vezf1 results in loss of DNA methylation at widespread sites in the genome, including Line1 elements and minor satellite repeats, some imprinted genes, and several CpG islands. Loss of methylation appears to arise from a substantial decrease in the abundance of the de novo DNA methyltransferase, Dnmt3b. These results suggest that naturally occurring mutations in Vezf1/BGP1 might have widespread effects on DNA methylation patterns and therefore on epigenetic regulation of gene expression.
Gowher
Humaira
H
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Stuhlmann
Heidi
H
Felsenfeld
Gary
G
D000818:Animals; D002460:Cell Line; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D014157:Transcription Factors; D014162:Transfection; D000097584:DNA Methyltransferase 3B
D004248:DNA (Cytosine-5-)-Methyltransferases; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; D000097584:DNA Methyltransferase 3B; C117684:Vezf1 protein, mouse