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. 2017 Mar 3;7:45. doi: 10.1038/s41598-017-00079-x

Figure 4.

Figure 4

ZEB1 promotes UM cell dedifferentiation by repressing the pigment synthesis pathway. A significant underexpression of genes involving in melanocyte differentiation such as (A) BAP1, (B) MITF, (C) TYR, and (D) TYRP1 was detected in UM and MetUM as compared to NUM. Higher expression of these differentiation genes was also detected in the spindle non-aggressive OCM1 as compared to the epithelioid aggressive C918. (E) ZEB1 was only detected in the epithelioid cells which manifested non- or less pigment in a representative patient UM section. An H&E stained section of the same area is included to show the mixed phenotype. Knockdown of ZEB1 significantly amplified transcription of all these differentiation genes in both (F) OCM1 and (G) C918. (H) ChIP assays showed that ZEB1 bound to MITF-M (melanocyte-specific) and BAP1 promoters, likely to repress their expression. Mean (M) ± standard deviation (SD). ‘*’ Indicates Student’s t-test p ≤ 0.05, ‘**’ Indicates Student’s t-test p ≤ 0.01.