id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-352219-z245sb3s	Tallam, Aravind	Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages	2016-02-12		.txt	text/plain	9117	467	43	Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Putative transcriptional regulators of IRG1 were hypothesized from the resulting GRN and tested using siRNA-mediated gene silencing experiments in mouse and human macrophages under LPS stimulation. Although the human data were obtained from primary cells, while the mouse analysis was conducted using the macrophage cell line RAW264.7, it is tempting to speculate that the transcriptional machinery inducing IRG1 expression, with the exception of IRF1, is mostly species-specific, as highlighted by the different transcriptional regulators identified in the two species (Table 1) .	./cache/cord-352219-z245sb3s.txt	./txt/cord-352219-z245sb3s.txt