Smale Stephen T, Fisher Amanda G
Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095-1662, USA.
Annu Rev Immunol. 2002;20:427-62. doi: 10.1146/annurev.immunol.20.100301.064739. Epub 2001 Oct 4.
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.
免疫系统的发育以及宿主对微生物感染的反应依赖于众多差异表达基因的激活和沉默。自20世纪80年代中期以来，一个主要目标一直是确定调控特定基因和特定免疫过程的转录因子。最近，人们越来越认识到染色质结构在基因调控中的作用。在大多数基因激活剂进入其结合位点之前，似乎会发生从浓缩染色质结构到解浓缩染色质结构的转变。转录激活随后伴随着特定核小体的重塑。相反，获得更浓缩的染色质结构通常与基因沉默相关。染色质结构是基因调控的一个特别重要的因素，因为它可能是细胞身份和细胞记忆的主要决定因素。也就是说，通过DNA复制和细胞分裂在特定位点传播解浓缩染色质有助于细胞记住哪些基因在该细胞类型中持续表达，或者在受到刺激时准备表达。在这里，我们综述了在理解染色质在免疫系统中的作用方面的最新进展。白细胞介素-4基因是探索获得和解浓缩染色质结构的可遗传维持所涉及事件的主要模型。然后综述了白细胞介素-12 p40和干扰素-β基因研究，以深入了解启动子附近特定核小体重塑有助于细胞刺激后快速激活的机制。最后，讨论了基因沉默的基本原理。
