Abstract
Transcriptional activation and repression of genes that are developmentally regulated or exhibit cell-type specific expression patterns is largely achieved by modifying the chromatin template at a gene locus. Complex formation of stable epigenetic histone marks, loss or gain of DNA methylation, alterations in chromosome conformation, and specific utilization of both proximal and distal transcriptional enhancers and repressors all contribute to this process. In addition, long non-coding RNAs are a new species of regulatory RNAs that either positively or negatively regulate transcription of target gene loci. IFN-γ is a pro-inflammatory cytokine with critical functions in both innate and adaptive arms of the immune system. This review focuses on our current understanding of how the chromatin template is modified at the IFNG locus during developmental processes leading to its transcriptional activation and silencing.
Highlights
Reviewed by: Urszula Krzych, Walter Reed Army Institute of Research, USA Beatrice Jahn-Schmid, Medical University of Vienna, Austria
This review focuses on our current understanding of how the chromatin template is modified at the IFNG locus during developmental processes leading to its transcriptional activation and silencing
Differentiated T cells, termed T helper 1 (Th1) and T cytotoxic 1 (Tc1) produce IFN-γ as their predominant cytokine in response to secondary antigenic stimulation. This differentiation process arises from marked epigenetic changes spanning a region greater than 100 kb surrounding the gene that encodes IFN-γ (Zhou et al, 2004; Chang and Aune, 2005; Schoenborn et al, 2007). These epigenetic changes include gain and loss of histone modifications associated with activation and silencing of gene transcription, respectively, changes in DNase hypersensitivity sites, and changes in methylation (Me) of CpG dinucleotides, a modification associated with transcriptional silencing
Summary
Transcriptional activation and repression of genes that are developmentally regulated or exhibit cell-type specific expression patterns is largely achieved by modifying the chromatin template at a gene locus. The IFNG locus undergoes complex patterns of histone modifications in response to Th1/Th2 differentiation signals (Zhou et al, 2004; Chang and Aune, 2005, 2007; Schoenborn et al, 2007).
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