Fig. 3

Regulation of HSC lncRNAs. a Conditions for HSC lncRNA analysis. HSC myofibroblasts were cultured for 48 h in 0.2 % bovine serum albumin to remove exogenous TGF-β from the media (low TGF-β) and then treated with TGF-β for 16 h to define lncRNAs regulated by TGF-β signaling. b lncRNA expression in response to TGF-β signaling. The heatmap shows normalized expression of lncRNAs that were induced (red) or repressed (green) in response to TGF-β signaling. The Z-score is shown on the right and was calculated from expression of lncRNAs in two replicates of low TGF-β conditions (not shown) and two replicates of TGF-β treatment (shown). Each row represents one lncRNA locus and lncRNA loci are ranked by p value such that the smallest p value of induced lncRNAs is at the top and the smallest p value of repressed lncRNAs is at the bottom. c The gene encoding lncRNA-000509 is occupied by SMAD3 and induced in response to TGF-β signaling. SMAD3 occupancy [90] is shown at the top. RNA-seq reads (red) are displayed for HSCs in low TGF-β and after 16 h of TGF-β signaling. The structure and direction of lncRNA-000509 is shown below. d lncRNAs that are regulated by TGF-β signaling tend to be occupied by SMAD3. The fraction of lncRNA genes that are induced (left) and repressed (right) by TGF-β and are occupied by SMAD3. Genes that are regulated in response to TGF-β signaling and occupied by SMAD3 are considered direct targets of TGF-β signaling. e lncRNAs directly targeted by TGF-β signaling tend to be associated with super-enhancers. lncRNA genes that change in expression in response to TGF-β signaling and are occupied by SMAD3 (Direct target) are associated with super-enhancers (Super-E), while lncRNAs that change in expression in response to TGF-β signaling and are not directly occupied by SMAD3 (Indirect target) are associated with typical enhancers (Typical E)