Zmiz1-dependent Native Stem Cell Transcriptional Circuits in Normal and Malignant Immature T cells [RNA-seq]

The discovery of early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) was based on expression of stem cell genes that are characteristic of mouse ETP cells, the most primitive multipotent cells in the thymus. Using complementary mouse and human genetic models and genome-wide expression and chromatin profiling integrated with 3D chromatin mapping, we show that the PIAS-like coactivator ZMIZ1 promotes immature T-ALL proliferation by recruiting the transcription factor MYB in feedforward circuits to cooperatively induce MYCN, MEF2C, and BCL2, which were recently associated with the high-risk bone marrow progenitor (BMP-like) subset. In the first experiment (Batch RS6) short hairpin RNAs shZMIZ1-13 (L13) and shZMIZ1-15 (L15) target the gene ZMIZ1 In the second experiment (Batch RS7) the gene MYB is knocked down.