Fig. 1: The interaction of bone marrow stroma and myeloma cells induces chromatin remodeling with altered accessibility in known cis-regulatory elements (CREs) in three myeloma cell lines.

a Experimental design to identify changes in chromatin accessibility and gene expression in three myeloma cell lines after 72 h of co-culture with bone marrow stromal cells. b Circular scatter plot showing regions with increased and decreased chromatin accessibility after stromal co-culture across the entire genome. There was widespread chromatin remodeling involving a large number of genomic regions with both increased and decreased chromatin accessibility. We used this approach as a first step to select 111217 candidate regions with altered chromatin accessibility after stromal co-culture. c Volcano plot showing differentially accessible genomic regions (FDR < 0.050). These 4511 differentially accessible regions represent a subset of the initially identified 111217 candidate regions. d Venn diagram demonstrating the overlap between the 4511 differentially accessible regions and three databases of annotated human cis-regulatory elements. e Euler diagrams and bar graph depicting the filtering and prediction strategy employed to associate the 4511 differentially accessible regions with potential target genes within previously described conserved myeloma-specific topologically associating domains (TADs)⁴⁸. After filtering, there were 4288 differentially accessible regions predicted to interact with 4626 potential target genes in close proximity. The 4288 differentially accessible regions were predicted to interact with either one or two potential target genes after applying all filtering criteria. f Position-specific weight matrices showing the top 3 transcription factors expected to bind in the genomic regions accessible after stromal co-culture (selected by transcription factor footprinting)⁵³. Motif enrichment analyses are also shown. Among the top enriched transcription factors were FOS, FOSL2, and KLF5. Source data are provided as a Source Data file.