Figure 3.
Genome-wide analysis of PBX1 function in chr1q-amp myeloma cells. (A) Heat map representation of PBX1 cistrome in MM.1S and U266 cells, as identified by ChIP-seq analysis (n = 2 per cell line). Genomic annotation (left) and epigenomic chromHMM states (right) of significantly enriched regions are also shown. (B) SE analysis across 9 MM cell lines and 8 MM primary samples using H3K27ac-seq (data obtained from Jin201834). Number of total and PBX1-bound SEs across 17 MM samples (left panel) and the aggregated profile in all samples (right panel) are shown. (C) Boxplot representations of average normalized H3K27ac signal of chr1q-amp and nonamplified samples across 1655 PBX1-bound SEs. Analysis was performed using a paired Student t test. (D) Pathway analysis of genes predicted to be regulated by PBX1-bound SEs in chr1q-amp (+) and nonamplified (-) cells. (E) Integrative cistrome-transcriptome analysis with BETA-plus displays the regulatory program of PBX1 in MM.1S cells. Biological annotation of genes was performed using the Molecular Signatures Database. Node colors represent average predicted activation (blue) or repression (red) for each gene. Transcriptional targets of interest are highlighted in red font. (F) Overrepresentation analysis against the ChEA database and NCI-Nature pathways of the direct PBX1 target genes in MM.1S (upper panels) and U266 (lower panels) cells. Terms of interest are highlighted in red font. metabol, metabolism; Rel., relative.