Extended Data Fig. 8: Tbx15 is derepressed in Kdm8 mutant cardiomyocytes and represses the expression of metabolic regulators.
From: KDM8 epigenetically controls cardiac metabolism to prevent initiation of dilated cardiomyopathy
a, qPCR of Tbx15 on ventricles of Kdm8fl/fl;Nkx2-5-Cre mutants at 2 months of age analyzed by two-tailed Student’s t-test. Error bars denote the mean + /- s.e.m. n = 5 hearts per group. b, qPCR of Tbx15 on cardiomyocytes (CMs) and non-CMs isolated from Kdm8fl/fl control and Kdm8fl/fl;Myh6-Cre mutants at 2 months of age. Error bars denote the mean + /- s.d. Data was analyzed by two-way ANOVA. n = 4 mice per group. c, Chromatin-bound factors that target genes dysregulated in ventricles of 2-month-old Kdm8 mutant hearts as per ChIP Enrichment Analysis (ChEA). A complete list of ChEA-identified factors interacting with genes dysregulated in Kdm8 mutant hearts is shown in Supplementary Table 3. Data was analyzed using ChEA. d. qPCR of TBX15 in HEK293T cells transfected with control or TBX15-His plasmids, analyzed by two tailed Student’s t-test. Error bars denote the mean + /- s.e.m. n = 3 wells per group. e. Gene ontology (GO) term enrichment amongst genes downregulated in response to TBX15 overexpression. Terms associated with mitochondrial metabolism are highlighted in grey boxes. Data was analyzed using DAVID v6.8 with Benjamini correction. f. Western blot of mitochondrial complex V (ATP5A) in whole ventricles at 2 months of age. g, Band intensity of complex V protein normalized to histone H3 (H3) (shown in f) and analyzed by two-tailed Student’s t-test. Error bars denote the mean + /- s.d. n = 4 and 5 mice per group.
