Regulation of CD4 T-cell differentiation and inflammation by repressive histone methylation

Repressive epigenetic modifications such as dimethylation and trimethylation histone H3 at lysine 9 (H3K9me2 and H3K9me3) and H3K27me3 have been shown to be critical for embryonic stem (ES) cell differentiation by silencing cell lineage-promiscuous genes. CD4(+) T helper (T-H) cell differentiation is a powerful model to study the molecular mechanisms associated with cellular lineage choice in adult cells. Naive T-H cells have the capacity to differentiate into one of the several phenotypically and functionally distinct and stable lineages. Although some repressive epigenetic mechanisms have a critical role in T-H cell differentiation in a similar manner to that in ES cells, it is clear that there are disparate functions for certain modifications between ES cells and T-H cells. Here we review the role of repressive histone modifications in the differentiation and function of T-H cells in health and disease.