Fig. 6

A gene interaction network identified by IPA from the E vs. H contrast and functionally annotated as “Hematological System Development and Function”. This gene network (Panel a) is centered on direct interactions of two transcription regulators [PPARG coactivator 1 alpha (PPARGC1A) and sirtuin 1 (SIRT1)] with several blood clotting factors [tissue factor pathway inhibitor (TFPI); coagulation factor II, thrombin (F2); coagulation factor XI (F11); protein C, in-activator of coagulation factors Va and VIIIa (PROC); and protein Z, vitamin K-dependent plasma glycoprotein (PROZ)] and with components of the glutathione transferase pathway (GSTA1, GSTA2, GSTO1, GSTZ1, MGST3, GPX3 and GPX8). Panel b shows 24 direct targets of SIRT1 that were identified by Ingenuity® Up-stream Regulator Analysis, which predicts activation of SIRT1 since 17 of its known direct targets are upregulated in embryos. Orange arrows show genes that are up-regulated by SIRT1, while blunt blue edges indicate inhibition of known target genes, as predicted by Ingenuity software. Blue blunt lines predicts that activated SIRT1 would lead to inhibition of four known targets [cadherin 2 (CDH2) or inhibition [cyclin dependent kinase inhibitor 2B (CDKN2B); fatty acid synthase (FASN); H2A histone family member Z (H2AFZ); and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)]. Dark grey arrows identify several SIRT1 target genes, where an effect could not be predicted by IPA