Targeting of de novo DNA methylation throughout the Oct-4 gene regulatory region in differentiating embryonic stem cells.

ABSTRACT: Differentiation of embryonic stem (ES) cells is accompanied by silencing of the Oct-4 gene and de novo DNA methylation of its regulatory region. Previous studies have focused on the requirements for promoter region methylation. We therefore undertook to analyse the progression of DNA methylation of the approximately 2000 base pair regulatory region of Oct-4 in ES cells that are wildtype or deficient for key proteins. We find that de novo methylation is initially seeded at two discrete sites, the proximal enhancer and distal promoter, spreading later to neighboring regions, including the remainder of the promoter. De novo methyltransferases Dnmt3a and Dnmt3b cooperate in the initial targeted stage of de novo methylation. Efficient completion of the pattern requires Dnmt3a and Dnmt1, but not

SUBMITTER: Athanasiadou R 

PROVIDER: S-EPMC2848578 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature