Genome-wide analysis identifies a functional association of Tet1 and Polycomb PRC2 in mouse embryonic stem cells but not in differentiated tissues
Recent studies have analyzed the distribution and role of 5-hydroxymethylcytosin (5hmC) in Embryonic Stem Cells (ESC). However, DNA hydroxymethylation occurs also in differentiated cells and it is significantly deregulated in cancer. Here we mapped 5hmC genome-wide profile in pluripotent ES cells in comparison to embryonic and adult differentiated cells. Comparative analysis of 5hmC genomic distribution with respect to gene expression reveals that 5hmC is enriched on the gene body of genes expressed at medium/high level and on TSS of genes not expressed or expressed at low level independently from the cell type. ESC showed a significant enrichment of DNA hydroxymethylation in active enhancers and bivalent promoters with respect to more differentiated cells as well as preferential association of Tet1 and 5hmC with promoter bound by Polycomb Repressive Complex 2 (PRC2). Furthermore, we show that in ESC PRC2 interacts with Tet1 and it is required for Tet1 recruitment to the chromatin and 5hmC deposition at developmental genes. Overall design: Examination of 5hmC in ESC, MEF, Brain, Liver, shGFP ESC, and shSuz12ESC, and examination of expression in shGFP ESC and shSuz12ESC.