Fig. 7: BNC2 controls the MF transcriptome, including fibrogenic ECM-related genes.

A Biological Process GO term enrichment analysis was performed using genes linked to the BNC2 cistrome. The main recovered terms are indicated under “BNC2 cistrome predicted targets”. Next, microarray-based analysis was used to define how BNC2 predicted target genes were deregulated upon BNC2 silencing. Dot plot depicts the results of GSEA performed for each term using transcriptomic changes induced by BNC2 silencing in LX2 cells, which were transfected with the BNC2-targeting siRNA (siBNC2) or a non-targeting control siRNA (siCTRL) (n = 4 biologically independent experiments). Dot areas are proportional to the normalized encrichment score (NES), while colors indicate the false discovery rate (FDR). A random list of 500 human genes was used as a negative control. B Genes both bound and regulated by BNC2, i.e., genes from the GSEA core enrichments from panel A, were further mined to search for enriched molecular pathways using ToppGene. Enriched terms were clustered according to the similarity of gene lists (Supplementary Fig. 12C), and main clusters pointing to related common molecular functions were further grouped. C, D Enrichment plots from GSEA performed using transcriptomic changes induced by siBNC2 in LX2 cells as the ranking measure and the Matrisome (ECM and ECM-associated genes, n = 1028; C) or human proteomics-based identified fibrotic liver ECM genes (n = 71; D) as the gene sets. NES and FDR are the normalized enrichment score and the false discovery rate provided by GSEA, respectively. E, F Enrichment plots from GSEA similar to those shown in (C, D) obtained using mining of transcriptomic data from EMS404 cells transfected using siBNC2 or siCTRL (control).