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. 2015 Sep 5;6(27):23058–23134. doi: 10.18632/oncotarget.5492

Figure 5. Transcriptional repression of Bim.

Figure 5

Several transcription factors prevent Bim transcription. Some of them, e.g., NFκB and E2F-1, play a dual role by regulating both Bim transactivation (Figure 4) and transrepression. The RelA component of NFκB acts as a transactivator in the absence of YY-1, while becomes a transrepressor in its presence. E2F1 may directly or indirectly transactivate Bim by inducing c-Myc and B-Myb expression (Figure 4), but, in addition, it induces the polycomb histone methyl transferase EZH2 that promotes trimethylation of Histone 3 on Lys27 (H3K27me3), leading to the repression of Bim expression. Spi-1/PU.1 and Trim33 cooperate with EZH2 to repress Bim transcription. Furthermore, E2F1 directly or through c-Myc induces miR106∼25 that prevents Bim translation (Figure 6). The multiple effects of E2F1 may ensure fine tuning of Bim expression. HIF-1α that is, among others, induced by hypoxic conditions within the tumor microenvironment, prevents Bim expression, thus providing a growth advantage to the tumor cells. Description of the other repressors can be found in Section 3.1.2.