GSE61360
Bap1 loss results in EZH2 dependent transformation
BAP1 and ASXL1 interact to form a polycomb deubiquitinase complex that removes monoubiquitin from histone H2A lysine 119 (H2AK119Ub). However, BAP1 and ASXL1 are mutated in distinct cancer types, consistent with independent roles in regulating epigenetic state and malignant transformation. Here we demonstrate that Bap1 loss results in increased trimethylated histone H3 lysine 27 (H3K27me3), elevated Ezh2 expression, and enhanced repression of Polycomb Repressive Complex 2 (PRC2) targets. These findings contrast with the reduction in H3K27me3 seen with Asxl1 loss. Conditional deletion of Bap1 and Ezh2 in vivo abrogates the myeloid progenitor expansion induced by Bap1 loss alone. Overall design: Whole bone marrow cells from mice treated with polyI:polyC at three weeks of age were extracted from Bap1 f/f  and Mx1-Cre negative Bap1f/f littermates. Bone marrow cells were red cell lysed and cells were sorted for granulocyte macrophage progenitors (GMP). Genomic DNA was extracted for ChIP-Seq studies to assess transcriptional changes with Bap1 loss in GMPs.