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.
Featured Papers
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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
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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
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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
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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