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. 2012 Jul 13;7(7):e40943. doi: 10.1371/journal.pone.0040943

Figure 6. A proposed working model to depict the process of how ATRA induces growth arrest in DU145 cells through upregulating HOXB13.

Figure 6

EZH2 directly binds onto the HOXB13 promoter and induces trimethylation of H3K27 to repress the HOXB13 expression. DNMT3b is recruited to HOXB13 promoter by EZH2 to induce the DNA hypermethylation resulting in further repression of the gene. Meanwhile, ATRA represses EZH2 and DNMT3b expression, and impairs their binding at HOXB13 promoter to decrease the methylation level of HOXB13 promoter, resulting in the activation of HOXB13, which in turn inhibits the growth of DU145 cells. Moreover, repression of DNMT3b also upregulates the RARβ expression, which may enhance the sensibility of the DU145 cells to ATRA. A combined treatment of both ATRA and 5-aza-dc brings about enhanced effects on HOXB13 upregulation and the inhibition of the growth of DU145 cells.