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. Author manuscript; available in PMC: 2022 Feb 1.
Published in final edited form as: Cancer Res. 2021 May 14;81(15):4001–4013. doi: 10.1158/0008-5472.CAN-20-2562

Figure 4: L-2HG drive hypoxia mediated epigenetic changes and regulate stemness and differentiation gene methylation status.

Figure 4:

Octyl L-2HG treatment (mM) results in increase in histone methylation (A). CHIP QPCR analysis showed that in hypoxic cells H3K9 was trimethylated at differentiation gene (PDX-1) promoter (B) and monomethylated in stemness gene (CD133) promoter (C). Similarly, Octyl L-2HG treated cells were trimethylated at PDX-1 promoter (D) and monomethylated at CD133 gene promoter (E). Silencing of LDH and MDH enzyme promote demethylation of histones as shown by western blot analysis under hypoxia (F). * indicate p-value </= 0.05. RNA seq analysis identified stemness pathways among top canonical pathways that were upregulated after treating MIA-PACA2 cells with L-2HG (G). Schematic diagram showing self-renewal and differentiation pathways identified in the RNA seq dataset (H).