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. Author manuscript; available in PMC: 2013 Jul 3.
Published in final edited form as: Cell Metab. 2012 Jul 3;16(1):9–17. doi: 10.1016/j.cmet.2012.06.001

Figure 4. Proposed model for the role of 2HG in epigenetic regulation and cell differentiation.

Figure 4

When progenitor cells differentiate, JHDM removes repressive histone methylation marks (H3K9me3 and H3K27me3) and activates the expression of differentiation-related genes. In addition, TET acts as a failsafe mechanism to protect promoters from aberrant DNA methylation. 2HG produced by mutant IDH inhibits JHDM and TET, which leads to histone and DNA hypermethylation and permanently “locks” differentiation-related genes in a silent state. This results in a differentiation arrest and expansion of progenitor cells, thus facilitating tumor development.