Chromatin immunoprecipitation and sequencing analysis of FOXP1 target genes. To identify direct FOXP1 target genes, we conducted genome-wide mapping of the FOXP1 binding sites in 4 DLBCL cell lines, by chromatin immunoprecipitation with a FOXP1-specific antibody followed by high-throughput sequencing (ChIP-seq). (A) A Venn diagram showing the number of genes in each cell line with a FOXP1 binding peak within 20 kb of the TSS, as determined by ChIP-seq. (B) Percentage of all expressed genes or FOXP1-regulated genes (as determined by microarray analysis) in a cell line that showed a FOXP1 binding peak within 2 kb or 20 kb of the TSS, as determined by ChIP-seq (left), and the percentage of genes being either up- or downregulated, among the genes that are both regulated and bound by FOXP1 within 20 kb of the TSS (right). (C) De novo motif analysis of FOXP1 ChIP-seq peaks in OCI-Ly3 reveals the presence of several enriched motifs in the FOXP1-binding regions. Relative enrichment to control regions and percentage of peaks containing the motif are shown. (D) Overlap of IRF4 ChIP-seq peaks and SpiB ChIP-seq peaks in HBL1³⁸  with FOXP1 ChIP-seq peaks in DLBCL cell lines. (E) The number of FOXP1 ChIP-seq peaks that were found exclusively either in both ABC-DLBCL cell lines (OCI-Ly3 and OCI-Ly10) or in both GC-DLBCL cell lines (OCI-Ly1 and OCI-Ly7) and the proportion of these peaks that were also found among IRF4 or SpiB ChIP-seq peaks in HBL1³⁸  or that contained a consensus NF-κB binding site. (***P < .001 significant difference between presence of SpiB or IRF4 peaks or a NF-κB consensus motif among ABC-specific vs GC-specific FOXP1 CHIP-seq peaks as determined by χ² test). (F) Tracks showing the locations of the FOXP1 ChIP-seq peaks in the proximity of the TSS of RASSF6, AIM2, and BIK, some of the proapoptotic genes that are downregulated by FOXP1 in primary human B cells and DLBCL cell lines.