Fig. 5

Integrity of the enhancer cluster RE6-9 is required for its function in the heart and cardiac Scn5a expression. a UCSC browser view of the enhancer cluster RE6-9 and the deletions of regulatory elements within this region by TALEN and CRISPR/Cas9 technology (red rectangles). Included location of the TALENs and CRISPR/Cas9 sgRNAs design and cardiomyocyte-specific H3K27ac ChIP³³. b Sequence traces of a genetic variant in Scn5a, Scn10a and Exog from SPRET;FVB and SPRET;FVB^ΔRE6-9 F1 hybrids. c Fold change expression level of Scn5a in different compartments of heart from 8-week old RE6-9^+/− mice compared to wildtype (WT). P values were calculated using unpaired Student’s t test. WT n = 4; RE6-9^+/− n = 5 (LA, RA, IVS); RE6-9^+/− n = 7 (LV, RV). **P < 0.01; ***P < 0.001. d Fold change expression level of Scn5a from left ventricle of 8-week old RE6-9^+/− and Scn5a^+/Δ7 mice. P values were calculated using unpaired Student’s t test. WT n = 4; Scn5a^+/Δ7 n = 4; RE6-9^+/− n = 5. *P < 0.05; **P < 0.01. e Fold change expression level of Nav1.5 from left ventricle of 8-week old RE6-9^+/− and Scn5a^+/Δ7 mice. WT n = 2; Scn5a^+/Δ7 n = 2; RE6-9^+/− n = 2. f Fold change expression level of Scn5a from various established mouse lines (8-week old) with deletions of regulatory elements from the enhancer cluster. P values were calculated using unpaired Student’s t test. T RE6-9^+/− n = 5; C1 RE6-9^+/− n = 7; C2 RE6-9^+/− n = 5; C3 RE6-9^+/− n = 3; C4 RE6-9^+/− n = 4; C1 RE9^+/− n = 6; C2 RE9^+/− n = 5; C3 RE9^+/− n = 4; C RE6-8^+/− n = 5; T RE6^+/− n = 5. *P < 0.05; ***P < 0.001. g Fold change expression level of Oxsr1, Exog, Scn5a, Scn10a, and Wdr48 of CRISPR transgenic mouse lines RE6-9, RE9, or RE6-8. P values were calculated using unpaired Student’s t test. *P < 0.05; **P < 0.01; ***P < 0.001. Bars represent mean ± SEM. LV left ventricle, RV right ventricle, IVS interventricular septum, LA left atrium, RA right atrium, T TALEN, C CRISPR/Cas9. Source data are provided as a Source Data file