Project description:CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) is a member of the CITED family of proteins that play very critical roles in cellular development and differentiation. Several independent studies have revealed that mutation in the CITED2 gene is associated with human congenital heart defects. Concordant with these observations, experimental murine studies affirmed that mutation or loss of Cited2 resulted in congenital heart defects, as well as perturbation in the left-right patterning of the body axis. Furthermore, deficiency of Cited2 significantly impaired the development of lung, liver, placenta, and adrenal tissue at the embryonic stage (PMCID: PMC5809687).
Project description:CITED2 is a member of the CBP/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain family of transcriptional regulators and is exclusively localized in the nucleus. Previous studies have demonstrated that CITED2 plays an important role in cellular development and differentiation. Experimental murine studies have shown that Cited2 mutation or deficiency results in congenital heart and neural crest defects, impairment in the development of lung, liver, placenta, and adrenal tissue, and perturbation in the left-right patterning of the body axis. Previous studies have also show that CITED2 is predominantly expressed in murine and human macrophages. Myeloid-specific CITED2 deficient mice are highly susceptible to lipopolysaccharide (LPS)-induced endotoxic shock syndrome, zymosan-induced lung inflammation, and experimental atherogenesis. Mechanistically, CITED2 in cooperation with PPARγ promotes anti-inflammatory gene expression while suppressing NFκB, HIF1α, STAT1, and IRF1 signaling to attenuate pro-inflammatory gene expression in macrophages.
Project description:Kruppel-like transcription factor 6 (KLF6) is a member of zinc-finger family transcription factors that regulate critical cellular processes including development, differentiation, proliferation, and programmed cell death. Alterations in KLF6 expression or function has been associated with the pathogenesis of numerous human ailments, including inflammatory bowel diseases, cancer, hepatic steatosis, and hepatic fibrosis.
Project description:BHLHE40 is a member of basic helix-loop-helix family transcription factors and highly conserved across mammalian species. Structurally, BHLHE40 consists of an N-terminal basic DNA binding domain, a helix-loop-helix dimerization domain, and a protein interacting orange domain. BHLHE40 is known to regulate a wide variety of essential cellular processes, including cell cycle, cellular proliferation, programmed cell death, cellular development and differentiation, and circadian rhythm. Here we isolated thioglycollate-elicited peritoneal macrophages (PMs) from 3 mice per group (Lyz2cre and Lyz2cre:BHLHE40Fl/Fl). These cells were stimulated with 100ng/ml LPS for 4 hours. Total RNA was isolated and subjected to RNAseq analyses.
Project description:Deletion of Arntl disrupted temporal inflammatory response in macrophage. Mechanistically, the acetylation status of lysine 27 of histone 3 (H3K27ac) was enhanced at the PU.1-containing enhancers in Arntl-/- macrophages compared to the wild-type cells. Collectively, transcription factor network containing Bmal1 controls temporal inflammatory response of macrophages by regulating epigenetic states of enhancers.