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Publication

Natural Genetic Variation Reveals Key Features of Epigenetic and Transcriptional Memory in Virus-Specific CD8 T Cells.

Immunity | 2019

Stable changes in chromatin states and gene expression in cells of the immune system form the basis for memory of infections and other challenges. Here, we used naturally occurring cis-regulatory variation in wild-derived inbred mouse strains to explore the mechanisms underlying long-lasting versus transient gene regulation in CD8 T cells responding to acute viral infection. Stably responsive DNA elements were characterized by dramatic and congruent chromatin remodeling events affecting multiple neighboring sites and required distinct transcription factor (TF) binding motifs for their accessibility. Specifically, we found that cooperative recruitment of T-box and Runx family transcription factors to shared targets mediated stable chromatin remodeling upon T cell activation. Our observations provide insights into the molecular mechanisms driving virus-specific CD8 T cell responses and suggest a general mechanism for the formation of transcriptional and epigenetic memory applicable to other immune and non-immune cells.

Pubmed ID: 31027997 RIS Download

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Associated grants

Agency: NHGRI NIH HHS, United States
Id: U01 HG007893
Agency: NCI NIH HHS, United States
Id: P30 CA008748
Agency: NIAID NIH HHS, United States
Id: R37 AI034206
Agency: NCI NIH HHS, United States
Id: U54 CA209975
Agency: Howard Hughes Medical Institute, United States

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