Fig. 9

Another gene network, functionally annotated by IPA as “Lipid Metabolism”, was identified in E18 vs. D3 contrast (a). This network shows interactions among six up-stream regulators [RAR related orphan receptor A (RORA), SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 3 (SMARCD3), ESRRG, NR1H4 (or farnesoid X receptor, FXR), PPARGC1A and SREBF2]. Ingenuity Upstream Regulator Analysis predicts inhibition of RORA (Panel b), since the majority of its target genes are down-regulated (green symbols) in the E18 vs. D3 contrast. The blue arrows directed at three lipogenic genes (FASN PLIN2 and SCD) predict inhibition by RORA. However, RORA and five direct targets (IGFBP1, LPIN2, PPARGC1A and AKR1D1) are up-regulated in the E18 vs. D3 contrast as indicated by red gene symbols. Further, Ingenuity predicts that NR1H4 would be slightly activated, which would lead to activation (orange arrows) of four target genes (CETP, LCAT, LIPC and PPARA), although seven target genes are actually expressed at higher levels in liver of E18 embryos