Ikaros mediates the DNA methylation-independent silencing of MCJ/DNAJC15 gene expression in macrophages
Year: 2015
Type: article
Abstract: MCJ (DNAJC15) is a mitochondrial protein that regulates the mitochondrial metabolic status of macrophages and their response to inflammatory stimuli. CpG island methylation in cancer cells constitutes the only mechanism identified for the regulation of MCJ gene expression. However, whether DNA methylation or transcriptional regulation mechanisms are involved in the physiological control of this gene expression in non-tumor cells remains unknown. We now demonstrate a mechanism of regulation of MCJ expression that is independent of DNA methylation. IFNγ, a protective cytokine against cardiac inflammation during Lyme borreliosis, represses MCJ transcription in macrophages. The transcriptional regulator, Ikaros, binds to the MCJ promoter in a Casein kinase II-dependent manner, and mediates the repression of MCJ expression. These results identify the MCJ gene as a transcriptional target of IFNγ and provide evidence of the dynamic adaptation of normal tissues to changes in the environment as a way to adapt metabolically to new conditions.
Source: Scientific Reports
DOI: 10.1038/srep14692
Authors: Nicolás Navasa, Itziar Martin-Ruiz, Estíbaliz Atondo, James D. Sutherland, Miguel Angel Pascual-Itoiz, Ana Carreras-González, Hooman Izadi, Julen Tomás-Cortázar, Furkan Ayaz, Natalia Martin-Martin, Iviana M Torres, Rosa Barrio, Arkaitz Carracedo, Elias R. Olivera, Mercedes Rincón, Juan Anguita
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: G3484426243, G4742137835, G5741487336, Control of Macrophage Responses to Borrelia Burgdorferi by IFNg, G613225415, Implication of energy sensing pathways in prostate cancer biology, G6399461178, Potencial diagnóstico y terapéutico del metabolismo en el cáncer de próstata, G6741125160, Metabolic requirements for prostate cancer cell fitness
OpenAlex ID: W1886671083