Project description:Pharmacological inhibition of chromatin co-regulatory factors represents a clinically validated strategy to modulate oncogenic signaling through selective attenuation of gene expression. Here, we demonstrate that CBP/EP300 bromodomain inhibition preferentially abrogates the viability of multiple myeloma cell lines. Phenotypic effects are preceded by the direct transcriptional suppression of the lymphocyte-specific transcription factor IRF4 and the subsequent down-regulation of the IRF4 transcriptional program. Ectopic expression of IRF4 antagonizes the phenotypic effects of CBP/EP300 bromodomain inhibition and prevents the suppression of the IRF4 target c-MYC. These findings suggest that CBP/EP300 bromodomain inhibition represents a viable therapeutic strategy for targeting multiple myeloma and other lymphoid malignancies dependent on the IRF4 network. A total of 13 ChIP-seq samples were sequenced. Samples were treated with control (DMSO) or test compound (2.5 uM SGC-CBP30 or 0.25uM CPI267203) for 6 hours. Signal from input samples was included to subtract background signal from each ChIP-seq sample. Antibodies used were against p300, H3K18ac, H3K27ac, or BRD4.
Project description:The goal of this gene expression study was to identify genes whose expression depends on the transription factor IRF4 by knocking down it's expression using shRNA in two IRF4+ myeloma cell lines. Keywords: time series design Two myeloma lines were analyzed over a time course of IRF4-targeted shRNA induction. There are 3 time courses: two using KMS12 (biological replicates) and one with SKMM1. Within each time course there are technical replicates.
Project description:ChIP-seq data for the transcription factors (TFs) IRF4, PU.1 and SPIB from the cell lines OCI-LY3, OCI-LY10 and H929, and BATF from the cell lines OCI-Ly3 and OCI-Ly10. In addition ChIP-seq for the TFs IRF4, PU.1 and SPIB from the cell line OCI-LY3 following transfections of scramble/SPIB-siRNA. ChIP-seq data for the transcription factors (TFs) IRF4, PU.1 and SPIB from the cell lines OCI-LY3, OCI-LY10 and H929, and BATF from the cell lines OCI-Ly3 and OCI-Ly10. In addition ChIP-seq for the TFs IRF4, PU.1 and SPIB from the cell line OCI-LY3 following transfections of scramble/SPIB-siRNA.
Project description:To identify IRF4 transcription factor binding on chromatin at 5' regulatory regions of genes in myeloma cell line models. Keywords: binding site identification design Formaldehyde cross-linked, sonicated chromatin is prepared from cell lines Kms12 (test) and Ly19 (control). Chromatin immunoprecipated with anti-IRF4 antibody is labeled with Cy5 and co-hybridized on Agilent Human Promoter Set arrays with chromatin immunoprecipated with normal sera labeled with Cy3 . Two biological replicates were performed for the Kms12 and Ly19 experiments.
Project description:Pharmacological inhibition of chromatin co-regulatory factors represents a clinically validated strategy to modulate oncogenic signaling through selective attenuation of gene expression. Here, we demonstrate that CBP/EP300 bromodomain inhibition preferentially abrogates the viability of multiple myeloma cell lines. Phenotypic effects are preceded by the direct transcriptional suppression of the lymphocyte-specific transcription factor IRF4 and the subsequent down-regulation of the IRF4 transcriptional program. Ectopic expression of IRF4 antagonizes the phenotypic effects of CBP/EP300 bromodomain inhibition and prevents the suppression of the IRF4 target c-MYC. These findings suggest that CBP/EP300 bromodomain inhibition represents a viable therapeutic strategy for targeting multiple myeloma and other lymphoid malignancies dependent on the IRF4 network.
Project description:The goal of this gene expression study was to identify genes whose expression depends on the transription factor IRF4 by knocking down it's expression using shRNA in two IRF4+ myeloma cell lines. Keywords: time series design