Natural genetic variation reveals key features of epigenetic and transcriptional memory in virus-specific CD8 T cells Journal Article


Authors: van der Veeken, J.; Zhong, Y.; Sharma, R.; Mazutis, L.; Dao, P.; Pe'er, D.; Leslie, C. S.; Rudensky, A. Y.
Article Title: Natural genetic variation reveals key features of epigenetic and transcriptional memory in virus-specific CD8 T cells
Abstract: Van der Veeken et al. use naturally occurring cis-regulatory variation in wild-derived inbred mouse strains to dissect mechanisms of stable and reversible gene regulation in CD8 T cells. Their findings reveal central roles for T-box and Runx transcription factors and suggest a general mechanism for the formation of transcriptional and epigenetic memory. © 2019 Elsevier Inc. 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. © 2019 Elsevier Inc.
Keywords: transcription; memory; epigenetic
Journal Title: Immunity
Volume: 50
Issue: 5
ISSN: 1074-7613
Publisher: Cell Press  
Date Published: 2019-05-21
Start Page: 1202
End Page: 1217.e7
Language: English
DOI: 10.1016/j.immuni.2019.03.031
PUBMED: 31027997
PROVIDER: scopus
PMCID: PMC7023907
DOI/URL:
Notes: Article -- Export Date: 3 June 2019 -- Source: Scopus
Altmetric
Citation Impact
MSK Authors
  1. Alexander Rudensky
    132 Rudensky
  2. Christina Leslie
    143 Leslie
  3. Yi Zhong
    15 Zhong
  4. Dana Pe'er
    61 Pe'er
  5. Roshan Sharma
    11 Sharma
  6. Linas Mazutis
    24 Mazutis
  7. The Phuong Dao
    3 Dao