The Histone H3 Lysine-27 Demethylase Jmjd3 Links Inflammation to Inhibition of Polycomb-mediated Gene Silencing.
From: Department of Experimental Oncology, European Institute of Oncology, Campus IFOM-IEO, Via Adamello 16, 20139 Milan, Italy.
Cell
- Publish Date: Sep 2007
- ISSN: 0092-8674
- Volume: 130
- Issue: 6
- Pages: 1083-94
- Medium: Print
- Language: English
- Citation (JAMA): De Santa Francesca, Totaro Maria Grazia, Prosperini Elena, et al. The Histone H3 Lysine-27 Demethylase Jmjd3 Links Inflammation to Inhibition of Polycomb-mediated Gene Silencing.. Cell Sep 2007;130:1083-94
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.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Bone Marrow Cells, Cell Differentiation, Cell Lineage, Cells, Cultured, Dealkylation, Enzyme Induction, Female, Gene Silencing, Histones, Homeodomain Proteins, Humans, I-kappa B Kinase, I-kappa B Proteins, Inflammation, Lipopolysaccharides, Lysine, Macrophages, Mice, Molecular Sequence Data, NF-kappa B, Nuclear Proteins, Oxidoreductases, N-Demethylating, RNA, Messenger, Repressor Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Stem Cells, Substrate Specificity, Transcription, Genetic, Transduction, Genetic
Check for Full Text / PubMed Unique Identifier (PMID): 17825402
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.