1. CREBBP regulates antigen processing and presentation gene enhancers.
CREBBP regulates antigen processing and presentation gene enhancers. A and B, Bar plots representing the relative expression of antigen presentation and MHC II genes in OCI-Ly18 (A) and MD901 (B) cells upon CREBBP depletion and treated with either a selective HDAC3 inhibitor (HDAC3i; 20 μmol/L) or a control compound (Ctrli), as compared with scramble shRNA–induced cells (set as 1, dotted lines). Bar graph represents mean and SEM. from three replicates. C and D, Bar plots representing the relative H3K27ac enrichment at enhancers of MHC II genes in OCI-Ly18 (C) and MD901 (D) cells upon CREBBP depletion and treated with either a selective HDAC3 inhibitor (HDAC3i; 20 μmol/L) or a control compound (Ctrli), as compared with scramble shRNA–induced cells (set as 1, dotted lines). Bar graph represents mean and SEM from three replicates. E and F, Quantification of HLA-DR measured by flow cytometry in shCREBBP or scramble-transduced lymphoma MD901 (E) and OCI-Ly18 (F) cells treated with either a selective HDAC3 inhibitor (HDAC3i; 20 μmol/) or a control compound (Ctrli). Cells were transduced with shRNAs for 3 days and then treated with compounds for 96 hours. The data was represented as mean ± SD. Statistical significance was determined by Student t test. *, significant difference between control compound-treated scamble or shCREBBP-transduced cells (P < 0.05). #, significant difference between control compound and selective HDAC3 inhibitor–treated cells (P < 0.05). G and H, Representative flow cytometry histograms showing cell surface level of MHC II molecule HLA-DR that were quantified in E and F. I and J, Bar plots showing the relative proliferation of T cells stimulated by shCREBBP or scramble-transduced lymphoma MD901 (I) or OCI-Ly18 (J) cells treated with either a selective HDAC3 inhibitor (HDAC3i; 20 μmol/L) or a control compound (Ctrli). The data indicate relative folds of T-cell proliferation, represented as ratio of fluorescence (560 nm/590 nm) from each treatments to that from scramble shRNA–transduced cells treated with control compound (set as 1, dotted lines). Statistical significance was determined by Student t test.
Yanwen Jiang et al. Cancer Discov 2017;7:38-53
©2017 by American Association for Cancer Research