Fig. 7: Schematic illustration of the model.
From: The tumor suppressor MIR139 is silenced by POLR2M to promote AML oncogenesis
In the top panel, the MIR139 silencing mechanism in MLL-AF9 AML is shown. MLL-AF9 recruits PRC2 to the promoter, E1, E2, and the TSS of the PDE2A locus. POLR2M is recruited to E1, E2, and the TSS. POLR2M silences the transcription of MIR139, while the transcription of the host gene is unaffected. In the bottom panel, the mechanism of transcriptional activation by PRC2 inhibition and POLR2M depletion is shown. POLR2M depletion and PRC2 inhibition by UNC1999, which abrogates POLR2M interaction with the enhancers, results in transcription of MIR139. Increased miR-139 levels results in downregulation of EIF4G2, PTPRT, and HPGD and lead to cell death of MLL-AF9 cells.
