Vezf1 regulates genomic DNA methylation through its effects on expression of DNA methyltransferase Dnmt3b

被引:38
作者
Gowher, Humaira [1 ]
Stuhlmann, Heidi [2 ]
Felsenfeld, Gary [1 ]
机构
[1] NIDDKD, Mol Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA
[2] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY 10021 USA
关键词
DNA methylation; BGP1; Vezf1; Dnmt3b;
D O I
10.1101/gad.1658408
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:2075 / 2084
页数:10
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