Chromatin structure and gene regulation in the immune system.
The development of the immune system and the host response to microbial infection rely on the activation and silencing of numerous, differentially expressed genes. Since the mid-1980s, a primary goal has been to identify transcription factors that regulate specific genes and specific immunological processes. More recently, there has been a growing appreciation of the role of chromatin structure in gene regulation. Before most activators of a gene access their binding sites, a transition from a condensed to a decondensed chromatin structure appears to take place. The activation of transcription is then accompanied by the remodeling of specific nucleosomes. Conversely, the acquisition of a more condensed chromatin structure is often associated with gene silencing. Chromatin structure is a particularly significant contributor to gene regulation because it is likely to be a major determinant of cell identity and cell memory. That is, the propagation of decondensed chromatin at specific loci through DNA replication and cell division helps a cell remember which genes are expressed constitutively in that cell type or are poised for expression upon exposure to a stimulus. Here we review recent progress toward understanding the role of chromatin in the immune system. The interleukin-4 gene serves as a primary model for exploring the events involved in the acquisition and heritable maintenance of a decondensed chromatin structure. Studies of the interleukin-12 p40 and interferon-beta genes are then reviewed for insight into the mechanisms by which the remodeling of specific nucleosomes in the vicinity of a promoter can contribute to rapid activation following cell stimulation. Finally, basic principles of gene silencing are discussed.
Smale
Stephen T
ST
Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095-1662, USA. steves@hhmi.ucla.edu
Fisher
Amanda G
AG
D000483:Alleles; D000818:Animals; D002843:Chromatin / Q000235:genetics*; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation; D020868:Gene Silencing; D005801:Genes, Homeobox; D006801:Humans; D007109:Immunity / Q000235:genetics*; D016899:Interferon-beta / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D051379:Mice; D018448:Models, Immunological; D005810:Multigene Family; D009707:Nucleosomes / Q000276:immunology; D011401:Promoter Regions, Genetic; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism
D002843:Chromatin; D016207:Cytokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494748:Gata3 protein, mouse; D009707:Nucleosomes; D015534:Trans-Activators; D018664:Interleukin-12; D015847:Interleukin-4; D016899:Interferon-beta