Research ArticlesImmunology

The epigenetic control of stemness in CD8+ T cell fate commitment

See allHide authors and affiliations

Science  12 Jan 2018:
Vol. 359, Issue 6372, pp. 177-186
DOI: 10.1126/science.aah6499

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Epigenetic modulation of effector T cells

The epigenetic states and associated chromatin dynamics underlying the initiation and maintenance of memory and effector CD8+ T cells are poorly understood. Pace et al. found that mice lacking the histone H3 lysine 9 methyltransferase Suv39h1 had markedly reduced antigen-specific effector CD8+ T cell responses to Listeria monocytogenes infection (see the Perspective by Henning et al.). Instead, CD8+ T cells in these mice were enriched for genes associated with naïve and memory signatures and showed enhanced memory potential and increased survival capacity. Thus, Suv39h1 marks chromatin through H3K9me3 deposition and silences memory and stem cell programs during the terminal differentiation of effector CD8+ T cells.

Science, this issue p. 177; see also p. 163


After priming, naïve CD8+ T lymphocytes establish specific heritable transcription programs that define progression to long-lasting memory cells or to short-lived effector cells. Although lineage specification is critical for protection, it remains unclear how chromatin dynamics contributes to the control of gene expression programs. We explored the role of gene silencing by the histone methyltransferase Suv39h1. In murine CD8+ T cells activated after Listeria monocytogenes infection, Suv39h1-dependent trimethylation of histone H3 lysine 9 controls the expression of a set of stem cell–related memory genes. Single-cell RNA sequencing revealed a defect in silencing of stem/memory genes selectively in Suv39h1-defective T cell effectors. As a result, Suv39h1-defective CD8+ T cells show sustained survival and increased long-term memory reprogramming capacity. Thus, Suv39h1 plays a critical role in marking chromatin to silence stem/memory genes during CD8+ T effector terminal differentiation.

View Full Text