TRPS1 is a lineage-specific transcriptional dependency in breast cancer [Seq]

We performed an unbiased cell viability-based pooled shRNA screen on 59 cell lines to identify novel epigenetic and transcriptional dependencies of multiple cancer types, including leukemia, neuroblastoma, breast, colorectal, prostate, and rhabdoid tumors. Here, we identified Tricho-Rhino-Phalangeal Syndrome Type I protein (TRPS1) as one of the most significant hits specific for breast cancer cell lines. Downregulation of TRPS1 resulted in cell cycle arrest and apoptosis increase in vitro and impaired tumorigenic capacity in vivo. We characterized TRPS1 genomic targets and protein interactome. We identified GATAD2B as an important partner of TRPS1, uncovering novel epigenetic network crucial for breast cancer cell survival. Bulk RNA-Seq: Gene expression analysis of 57 cell lines used in the screen and HCC3153 and SUM159 cell lines with TET-inducible shRNA against TRPS1 with the following variables: Two different shRNA labeled sh1 (sh41) and sh2 (sh43), doxycyclin (plus/treatment) and no doxycyclin (minus/control), 3, 4 and 5 days after doxycyclin treatment. All conditions were sequenced without replicates (24 samples). ChIP-Seq: Examination of H3K27me3, GATAD2A, GATAD2B, H3K27ac, and TRPS1 in three different cell lines, in duplicates. HCC3153 cell line included the following variables: Two different shRNA labeled sh1 (sh41) and sh2 (sh43), doxycyclin (plus/treatment) and no doxycyclin (minus/control). Please note that the 'DFCI_EpiCluster_RNA-Seq.reads.gct' processed data file includes 4 re-analyzed samples, which were submitted as a part of series GSE63582 and the data columns correspond to the following samples; SUM149PT - GSM1842497 [SUM149_DMSO_12H_R1] SUM149PT_JQ1R_w_JQ1 - GSM1842493 [SUM149R_DMSO_12H_R1] SUM159PT - GSM1553156 [SUM159_DMSO_3H_1] SUM159PT_JQ1R_w_JQ1 - GSM1553147 [SUM159R_DMSO_3H_2]