Article

The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing.

Department of Experimental Oncology, European Institute of Oncology, Campus IFOM-IEO, Via Adamello 16, 20139 Milan, Italy.
Cell (Impact Factor: 33.12). 10/2007; 130(6):1083-94. DOI: 10.1016/j.cell.2007.08.019
Source: PubMed

ABSTRACT Epigenetic chromatin marks restrict the ability of differentiated cells to change gene expression programs in response to environmental cues and to transdifferentiate. Polycomb group (PcG) proteins mediate gene silencing and repress transdifferentiation in a manner dependent on histone H3 lysine 27 trimethylation (H3K27me3). However, macrophages migrated into inflamed tissues can transdifferentiate, but it is unknown whether inflammation alters PcG-dependent silencing. Here we show that the JmjC-domain protein Jmjd3 is a H3K27me demethylase expressed in macrophages in response to bacterial products and inflammatory cytokines. Jmjd3 binds PcG target genes and regulates their H3K27me3 levels and transcriptional activity. The discovery of an inducible enzyme that erases a histone mark controlling differentiation and cell identity provides a link between inflammation and reprogramming of the epigenome, which could be the basis for macrophage plasticity and might explain the differentiation abnormalities in chronic inflammation.

0 Followers
 · 
127 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The current epidemic of obesity and cardiometabolic diseases in developing countries is described as being driven by socioeconomic inequalities. These populations have a greater vulnerability to cardiometabolic diseases due to the discrepancy between the maternal undernutrition and its consequence, low-birth weight progeny, and the subsequent modern lifestyles which are associated with socioeconomic and environmental changes that modify dietary habits, discourage physical activity and encourage sedentary behaviors. Maternal undernutrition can generate epigenetic modifications, with potential long-term consequences. Throughout life, people are faced with the challenge of adapting to changes in their environment, such as excessive intake of high energy density foods and sedentary behavior. However, a mismatch between conditions experienced during fetal programming and current environmental conditions will make adaptation difficult for them, and will increase their susceptibility to obesity and cardiovascular diseases. It is important to conduct research in the Latin American context, in order to define the best strategies to prevent the epidemic of cardiometabolic diseases in the region.
    BMC Medicine 12/2015; 13(1). DOI:10.1186/s12916-015-0293-8 · 7.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Macrophages are essential components of the inflammatory microenvironment of tumors. Conventional treatment modalities (chemotherapy and radiotherapy), targeted drugs, antiangiogenic agents, and immunotherapy, including checkpoint blockade, all profoundly influence or depend on the function of tumor-associated macrophages (TAMs). Chemotherapy and radiotherapy can have dual influences on TAMs in that a misdirected macrophage-orchestrated tissue repair response can result in chemoresistance, but in other circumstances, TAMs are essential for effective therapy. A better understanding of the interaction of anticancer therapies with innate immunity, and TAMs in particular, may pave the way to better patient selection and innovative combinations of conventional approaches with immunotherapy. © 2015 Mantovani and Allavena.
  • [Show abstract] [Hide abstract]
    ABSTRACT: One of the best-characterized and biologically important gene expression programmes in myeloid cells is their response to pro-inflammatory stimuli. Macrophages and DCs in particular are key mediators of immune responses, and are widely-used as prototypes to understand and define the determinants of specific and inducible gene expression. In this review we summarize advances and concepts which have been made towards the understanding of inducible gene expression, with a particular focus on insights gained using the myeloid system as a model. We discuss the emerging concept of layered control of gene regulation and cell identity by different functional classes of transcription factors; and examine recent progress to understanding the molecular processes involved, including the involvement of nucleosome positioning, chromatin modifications, and nuclear architecture. We also address the exciting but less-well understood role of non-coding RNAs in controlling specific gene expression programmes in myeloid and other cell-types. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Seminars in Immunology 03/2015; DOI:10.1016/j.smim.2015.02.004 · 6.12 Impact Factor

Full-text (2 Sources)

Download
175 Downloads
Available from
Jun 2, 2014