Removal of DNA methylation is important for resetting chromatin to a pluripotent state. Jianlong Wang, Ph.D., at the Icahn School of Medicine at Mount Sinai, and colleagues recently published a report in Nature indicating that methyl groups are actively removed from DNA as part of the reprogramming process. Dr. Wang’s group isolated protein complexes containing NANOG, one of the key pluripotency factors, and used mass spectroscopy to refine the NANOG interactome. Amongst the proteins identified were TET1 and TET2, members of a family of proteins that convert methylcytosine to hydroxymethylcytosine, an intermediate along the pathway of methyl group removal from DNA. Based on several lines of evidence, it appears that NANOG recruits TET proteins to target genes, where they induce demethylation of the DNA, priming the genes for activation during establishment of pluripotency. This, along with several other recent papers, leads to the conclusion that removal of DNA methylation is not a passive result of DNA replication during cell division, but an active process inherent in reprogramming. This work was supported in part by a NYSTEM IDEA award to Dr. Wang (C026420).
Costa Y, Ding J, Theunissen TW, Faiola F, Hore TA, Shliaha PV, Fidalgo M, Saunders A, Lawrence M, Dietmann S, Das S, Levasseur DN, Li Z, Xu M, Reik W, Silva JC, Wang J. NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature. 2013 Mar 21;495(7441):370-4.