Chromatin Remodelling: Distinct Molecular Events During Differentiation and Activation of T Cells

Abstract

T lymphocytes undergo a complex series of developmental events in the thymus to become mature but naive circulating T cells. These naive T cells are activated during the response to pathogens to produce immune mediators and undergo further differentiation to give rise to distinct types of effector or memory cells. Each of these differentiation and activation events leads to major changes in gene expression patterns. The chromatin structure across a gene is one of the underlying mechanisms that determine its expression level in a specific cell type or in response to an activating signal. The changes in chromatin structure that occur across specific gene loci during differentiation and activation of T cells have been studied in detail in recent years and in many cases, they provide paradigms for the role of chromatin in differentiation and activation in other cell systems. Epigenetic marking and chromatin structure can be viewed as reversible or irreversible states and both appear to play major roles in controlling gene expression patterns in T cells. Reversibility is important for the quick response of cells to their environment, while irreversibility serves to lock in the specific patterns of gene expression that define distinct cell lineages. Changes in the modification state of histone proteins, the strength of histone: DNA contact, the methylation status of the DNA and nuclear location, all serve to determine chromatin structure and accessibility. Here we review the role of chromatin remodelling and epigenetic marking in regulating patterns of T cell gene expression. © 2006 Bentham Science Publishers Ltd.