Interplay between Chromatin Remodeling and Epigenetic Changes during Lineage-Specific Commitment to Granzyme B Expression

The role of chromatin remodeling and histone posttranslational modifications and bow they are integrated. to control gene expression during the acquisition of cell-specific functions is poorly understood. We show here that following in vitro activation of CD4(+) and CD8(+) T lymphocytes, both cell types show rapid histone H3 loss at the granzyme B (gzmB) proximal promoter region. However, despite the gzmB proximal promoter being remodeled in both T cell subsets, only CD8(+) T cells express high levels of gzmB and display a distinct pattern of key epigenetic marks, notably differential H3 acetylation and methylation. These data suggest that for high levels of transcription to occur a distinct set of histone modifications needs to be established in addition to histone loss at the proximal promoter of gzmB. The Journal of Immunology, 2009, 183: 7063-7072.