Anne-Marie Koop

7 269 Figure 5 a 0 20 40 60 80 -20 -10 0 10 Gm10718 Esr1 Nebl Aspn Mier1 Xlr3b Gm6211 Fmo2 Ankrd1 Exoc5 Ifi205 Ccdc152 Dynlt3 Rps6ka3 Stag2 Hdx Prkg1 Thoc2 Arhgap5 Mgam Vps13a Hnrnpa3 Kif5b Cdc73 Myo9a Sh3bgrl Mul1 Rock2 Gm2788 Rab11b Pkig Lingo Hcn4 Gm26316 Mmp15 Hist1h4h Cav1 Tmem160 Zbed5 Gm10819 Arhgdia Ccdc85c Ccl5 Gm4604 Hspb7 Uqcrq Gpnmb Rnu3a Scarna2 Gm29667 Gm12416 Gm14111 Snord15a Gm6560 Gins2 Adam8 Gm26035 Mov10I1 Fitm1 Gm9824 Efnb3 Gm13192 Scarna6 Snord17 Gm24447 Gm26315 Gm26448 Atp5g3 Rn7s2 Gm11273 Atp5l2-ps Gm10566 Gm7331 Irf2bpl Gm26461 Lbh Cacna1g Oaz2 Gm27927 Gm25835 Gm5514 b Gm11249 Rmrp Rnu3b2 transcription factor activity sckeletal muscle cell differentiation response to cytokine regulation of transcription regulation of keratinocyte differentiation protein transporter activity positive regulation by host of viral process nucleus nucleic acid binding negative regulation of protein import muscle cell differentiation mitotic sister chromatid cohesion methylated histone binding metal ion binding intracellular core promoter sequence-specific DNA binding cohesin complex chondroitin sulfate metabolic process cellular response to hypoxia axon ensheathment c Tecrl,Gm15626 Gm10800 Gm10801 Gm21738 Ogn Hsp90aa1 Rnu3b1 Rnu3b4 Ucp3 Vaultrc5 Hand2 Dynll2 Nphs1 Gm4613 Ubc Gm26566 PAB: Hand2 F/F vs MCM-Hand2 F/F log10 ( p value) log2 (fold change) MCM-Hand2 F/F Hand2 F/F -1 -0.5 0 0.5 1 1.5 rich factor 0.2 0.4 0.6 0.8 100 200 300 1.5e-03 1e-03 2e-03 5e+04 p value nrofgenes starch and sucrose metabolism small cell lung cancer RNA transport protein processing in endoplasmic reticulum protein export progesterone-mediated oocyte maturation platelet activation oocyte meiosis p53 signaling pathway prostate cancer longevity regulating pathway- mammal long-term potentiation long-term depression gap junction Fanconi anemia pathway estrogen signaling pathway colorectal cancer cholinergic synapse pathways in cancer amphetamine addiction 5 10 15 20 25 0.04 0.03 0.02 0.01 rich factor 0.08 0.10 0.12 0.14 p value nrofgenes GO enrichment Pathway enrichment PAB Figure 5 . Hand2-dependent transcriptional changes in the pressure-overloaded RV. RNA-sequencing was performed to assess the transcriptomic changes in RV tissue from control (Hand2F/F) and knockout (MCM-Hand2F/F) animals subjected to PAB. a) Volcano plot representation of differential expression of genes in the RV of Hand2F/F versus MCM-Hand2F/F. Red and blue points mark the genes with significantly increased or decreased expression, respectively (FDR<0.01). The x-axis shows log2fold-expression changes and the y-axis the log10fold-likelihood of a gene being differentially expressed; b) Heatmap of the 100 top differentially expressed genes in the RV tissue of Hand2F/F sham compared to Hand2F/F PAB showing log2 FPKM (color scale) values of dysregulated genes, with red and blue colors representing increased