Cytosine Modifications in Development and Stem Cells
Methylation of cytosine to form 5-methylcytosine (5mC) on genomic DNA plays important roles in regulating gene expression. Although DNA methylation has been well studied, the reverse process has only recently been revealed in mammalian cells. A group of iron (II)/αKG-dependent dioxygenases, the TET proteins, oxidize 5mC to 5-hydroxymethylcytosine (5hmC), and then to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). The resulting 5fC and 5caC can be recognized by mammalian DNA glycosylase, thymine DNA glycosylase (TDG), in a base excision repair process to convert back to cytosine, providing an active demethylation pathway.
In collaboration with Dr. Chuan He at U. Chicago, we developed a suite of new technologies to map the genome-wide distribution of these modified cytosines and study the active demethylation process. These methods provide the community the tools to investigate 5mC oxidation and active DNA demethylation.
Song, C.X., Szulwach, K.E., Fu, Y., Dai, Q., Yi, C., Li, X., Li, Y., Chen, C.H., Zhang, W., Jian, X., Wang, J., Zhang, L., Looney, T.J., Zhang, B., Godley, L.A., Hicks, L.M., Lahn, B.T., Jin, P.*, and He, C*. (2010) A Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nature Biotechnology, 29(1): 68-72. (*:Co-Corresponding authors) PMC3107705
Yu, M., Hon, G.C., Szulwach, K.E., Song, C.X., Zhang, L., Kim, A., Li, X., Dai, Q., Shen, Y., Park, B., Min, J.H., Jin, P. *, Ren, B. *, and He. C. * (2012) Base-Resolution Analysis of 5-Hydroxymethylcytosine in the Mammalian Genome. Cell, 149: 1368-1380. (*: Co-Corresponding authors). PMC3589129
Song, C.X., Szulwach, K.E., Dai, Q., Fu, Y., Mao, S.Q., Lin, L., Street, C., Li, Y., Poidevin, M., Wu, H., Gao, J., Liu, P., Li, L., Xu, G.L., Jin, P.*, and He, C.* Genome-wide Profiling of 5-Formylcytosine reveals its roles in epigenetic priming. Cell, 153: 678-691. (*:Co-Corresponding authors) PMC3657391
Wang, T., Wu, H., Li, Y., Szulwach, K.E., Lin, L., Li, X., Chen, I.P., Goldlust, I.S., Chamberlain, S.J., Ananiev, G., Mowrey, J., Han, J.W., Yoon, Y., Rudd, M.K., Song, C.X., He, C., Chang, Q., Warren, S.T., and Jin, P. (2013) Subtelomeric hotspots of aberrant 5-hydroxymethylcytosine-mediated epigenetic modifications during reprogramming to pluripotency. Nature Cell Biology, 15: 700-711. PMC3998089