Fig. 7
The alternative pathway of bile acid synthesis is controlled by high regulatory load on CYP27A1 gene. a The mean normalized expression values of the genes implicated in the bile acid synthesis pathway based on the microarray data across the four differentiation time points are depicted. High regulatory load genes (CYP27A1 and ACP2) are presented in different shades of orange and with a thicker line than other genes of the pathway. b For each gene of the bile acid synthesis pathway, the rank of the expression level in the macrophage samples among the 188 conditions and cell types of the Primary Cell Atlas are shown by an orange or gray star (*) for high regulatory load genes and genes that are not under high regulatory load, respectively. Genes in the top ranks are situated in the top of the figure. c The expression profile for CYP27A1 across all 188 conditions and cell types from Primary Cell Atlas as arbitrary expression units. Macrophage samples are depicted in red. d The alternative pathway of bile acid synthesis was visualized in Cytoscape. To allow the alternative pathway to carry a flux, an exchange reaction was added, enabling the export of the last metabolite from the cell. Reactions predicted active in this modified macrophage model (day 11) are depicted as filled black circles or filled orange circles for reactions under control of high-regulatory load genes. The size of the nodes correlates with the number of associated enhancers. The reaction names correspond to reaction-identifiers of Recon 2. e The normalized expression levels of CYP27A1 in microarray analysis of THP-1 monocytes in a series of knock-down experiments for 53 different transcription factors or regulators and three unspecific control siRNAs retrieved from the FANTOM consortium database. Expression values were normalized to the first control siRNA (siNC) and represent the mean expression values ± SD (n ≥ 3). Student’s t-test determined the significance of changes in response to siRNA transfection (*, p <0.05; **, p <0.01)