MYC deregulates TET1 and TET2 expression to control global DNA (hydroxy)methylation and gene expression to maintain a neoplastic phenotype in T-ALL

We performed methylation, hydroxymethylation, and gene expression profiling using MeDIP-seq, hMeDIP-seq, and RNA-seq, respectively, to investigate the role of TET1 and TET2 in MYC-driven tumor maintenance. We compared T-ALL tumor cells before and upon MYC inactivation and revealed genome-wide changes in the DNA methylation and hydroxymethylation patterns. Furthermore, TET1 knock-down or ectopic TET2 expression in T-ALL revealed genome-wide changes in DNA methylation and hydroxymethylation patterns corresponding to changes in gene expression. Overall design: Samples used in this study correspond to T-cell acute lymphoblastic leukemia (T-ALL) cell lines derived from EµSRa-tTA;tet-o-MYC mice (6780) and human CCRF-CEM.