Ikaros Mediates the DNA Methylation-independent Silencing of MCJ/DNAJC15 Gene Expression in Macrophages

Overview

Journal Sci Rep

Specialty Science

Date 2015 Oct 1

PMID 26419808

Citations 10

Authors

Nicolas Navasa

Itziar Martin-Ruiz

Estibaliz Atondo

James D Sutherland

Miguel Angel Pascual-Itoiz

Ana Carreras-Gonzalez

Hooman Izadi

Julen Tomas-Cortazar

Furkan Ayaz

Natalia Martin-Martin

Iviana M Torres

Rosa Barrio

Arkaitz Carracedo

Elias R Olivera

Mercedes Rincon

Juan Anguita

Affiliations

Soon will be listed here.

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.

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