(A) Colon cancer cells were treated with IL-22 for 48 hours. Histone modifications were analyzed by Western blotting.
(B, C) Colon cancer sphere assay was performed in the presence of IL-22 and the DOT1L inhibitor EPZ004777. Sphere numbers were recorded. DLD-1 cells (B), primary colon cancer cells (C). (n = 5, P < 0.05).
(D, E) Colon cancer cells were cultured for 12 hours with IL-22. Expression of the genes encoding members of the DOT1L complex was quantified by real-time PCR. DLD-1 cells (D), primary colon cancer cells (E). (n = 3, P < 0.05).
(F) Colon cancer sphere assay was performed with colon cancer cells expressing sh-DOT1L or vector in the presence of IL-22. Sphere numbers were recorded. (n = 5, P < 0.05).
(G-I) H3K79me2-ChIP assay was performed to examine H3K79me2 at the core stem cell genes promoters in DLD-1 colon cancer cells cultured with IL-22. One of 3 experiments is shown.
(J-L). H3K79me2 ChIP was performed to examine occupancy at core stem cell genes in DLD-1 colon cancer cells cultured with or without IL-22 and EPZ004777. One of three experiments is shown.
(M) IL-22 (0.5ug) was injected into the DLD-1 tumor. After 12-48 hours tumor tissues were extracted for Western blotting analysis for the STAT3, H3K79me2, SOX2 and NANOG proteins. One of 3 experiments with triplicate sections is shown.