Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis (ChIP-seq)

ABSTRACT: DNA methylation is tightly regulated throughout mammalian development and altered methylation patterns are a hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in acute myeloid leukemia (AML) and has been suggested to protect CpG islands and promoters from aberrant methylation. By generating a novel mouse model of Tet2-deficient AML we show that loss of Tet2 in hematopoietic cells leads to progressive hypermethylation of active enhancer elements and altered expression of genes implicated in tumorigenesis. In contrast, CpG island and promoter methylation does not change in a Tet2-dependent manner. Furthermore, we confirm this specific enhancer hypermethylation phenotype in human AML patients. Thus, we propose that TET2 prevents leukemic transformation of hematopoietic cells by protecting enhancers from aberrant DNA methylation. ChIP-seq analysis for distribution of H3K4me1, H3K27ac, and H3K4me3 histone marks in in vitro-grown hematopoietic cells transduced with AML1-ETO

ORGANISM(S): Mus musculus

SUBMITTER: Kasper Rasmussen 

PROVIDER: E-GEOD-59580 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress