Abstract
It has been well documented that active genes, and their promoters and enhancers have a different chromatin or epigenomic environment compared with unexpressed genes. In addition, the epigenome may influence not only which genes are expressed, but also which genes can be induced in response to activation or differentiation signals. Immune cells respond to activation signals by rapidly inducing the expression of specific gene sets, and therefore this is a good system in which to examine the role of the epigenome in gene activation and cell differentiation. Several studies have now found that many immediate-early inducible genes exist in a similar epigenomic environment to active genes even in the unstimulated state. Some studies suggest that subsets of these genes may even have RNA polymerase II at their promoters and induction may be controlled downstream of its recruitment. Other inducible genes, however, undergo changes to histone modifications, levels or variant composition upon activation. In this article, we discuss how the epigenome of immune cells regulates inducible gene expression and discuss the differences between the immediate responses to activation signals and the longer term changes observed during differentiation.
Acknowledgements
The authors would like to thank Hugh French and Melanie Morris for useful discussions.
Financial & competing interests disclosure
Research in the authors laboratory is supported by grants from the National Health and Medical Research Council of Australia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Notes
ChIP: Chromatin immunoprecipitation; ChIP-chip: ChIP paired with genomic microarrays; ChIP-PET: ChIP paired end ditag sequencing; ChIP-seq: ChIP with massively parallel sequencing; GMAT: Genome-wide mapping technique; qRT-PCR: Quantitative real-time PCR; SACO: Serial analysis of chromatin occupancy; SAGE: Serial analysis of gene expression.
CTL: Cytotoxic T lymphocytes; HSC: Hematopoietic stem cell; Th: T helper; Treg: Regulatory T cell.
APC: Antigen-presenting cell; NFAT: Nuclear factor of activated T cells; PKC: Protein kinase C; TCR: T-cell receptor.