Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

SPIB and BATF provide alternate determinants of IRF4 occupancy in Diffuse Large B-cell Lymphoma linked to disease heterogeneity

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Matthew Care

PROVIDER: E-GEOD-56857 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

SPIB and BATF provide alternate determinants of IRF4 occupancy in diffuse large B-cell lymphoma linked to disease heterogeneity.

Care Matthew A MA Cocco Mario M Laye Jon P JP Barnes Nicholas N Huang Yuanxue Y Wang Ming M Barrans Sharon S Du Ming M Jack Andrew A Westhead David R DR Doody Gina M GM Tooze Reuben M RM

Nucleic acids research 20140529 12

Interferon regulatory factor 4 (IRF4) is central to the transcriptional network of activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL), an aggressive lymphoma subgroup defined by gene expression profiling. Since cofactor association modifies transcriptional regulatory input by IRF4, we assessed genome occupancy by IRF4 and endogenous cofactors in ABC-DLBCL cell lines. IRF4 partners with SPIB, PU.1 and BATF genome-wide, but SPIB provides the dominant IRF4 partner in this context. Upon ...[more]

PMID: 24875472

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Project description:The activated B cell-like (ABC) subgroup of diffuse large B cell lymphoma (DLBCL) is characterized by constitutive activation of the NF-ÃªB pathway. Here we show that the NF- ÃªB pathway induces the expression of the cytokines IL-6 and IL-10 in ABC DLBCL cell lines, which also have high levels of total and phosphorylated STAT3 protein, suggesting autocrine signaling. Using RNA interference for STAT3, we defined a gene expression signature of IL-6 and IL-10 signaling through STAT3. Based on this signature, we constructed a molecular predictor of STAT3 signaling that defined a subset of ABC DLBCL tumors with high expression of STAT3, IL-6 and/or IL-10, and their downstream targets. Although the STAT3-high and STAT3-low subsets had equivalent expression of genes that distinguish ABC DLBCL from GCB DLBCL, STAT3-high ABC DLBCLs had higher expression of signatures that reflected NF-kB activity, proliferation, and glycolysis. A smallmolecule inhibitor of JAK signaling, which blocked STAT3 signature expression, was toxic only for ABC DLBCL lines, and synergized with an inhibitor of NF-kB signaling. These findings suggest that the biological interplay between the STAT3 and NF-kB pathways may be exploited for the treatments of a subset of ABC DLBCLs. Activated B cell-like (ABC) subgroup of diffuse large B cell lymphoma (DLBCL) cell lines were used as model systems to study the cytokine pathways in these cells. We expressed inducible IkB super-repressor for 1 to 24 hours to identify NF-kB target genes in OCI-Ly3 and OCI-Ly10 cells for a total of 13 arrays with replicates of each time point. We treated OCI-Ly3 cells with IL-10 for 1 to 96 hours for a total of 10 arrays with replicates of each time point. We treated OCI-Ly10 cells with IL-6 for 30 minutes to 24 hours for a total of 8 arrays with replicates of each time point. OCI-Ly10 cells transfected with no siRNA versus STAT3-siRNA for 8, 24, or 48 hours for a total of 5 arrays with replicates for 24 and 48 hours. We treated OCI-Ly10 cells with JAK inhibitor I for 3 and 6 hours for a total of 4 arrays with replicates of each time point.

Dataset Information

SPIB and BATF provide alternate determinants of IRF4 occupancy in Diffuse Large B-cell Lymphoma linked to disease heterogeneity

Publications

SPIB and BATF provide alternate determinants of IRF4 occupancy in diffuse large B-cell lymphoma linked to disease heterogeneity.

Similar Datasets

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