title: Chromatin structure and gene regulation in the immune system.
abstract: 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.
authors.affiliation: 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
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Smale
authors.forename: Amanda G
authors.initials: AG
authors.lastname: Fisher
mesh_terms: 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
chemical_list: 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