TY - JOUR
T1 - CD8+ T Cells Utilize Highly Dynamic Enhancer Repertoires and Regulatory Circuitry in Response to Infections
AU - He, Bing
AU - Xing, Shaojun
AU - Chen, Changya
AU - Gao, Peng
AU - Teng, Li
AU - Shan, Qiang
AU - Gullicksrud, Jodi A.
AU - Martin, Matthew D.
AU - Yu, Shuyang
AU - Harty, John T.
AU - Badovinac, Vladimir P.
AU - Tan, Kai
AU - Xue, Hai Hui
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/12/20
Y1 - 2016/12/20
N2 - Differentiation of effector and memory CD8+ T cells is accompanied by extensive changes in the transcriptome and histone modifications at gene promoters; however, the enhancer repertoire and associated gene regulatory networks are poorly defined. Using histone mark chromatin immunoprecipitation coupled with deep sequencing, we mapped the enhancer and super-enhancer landscapes in antigen-specific naive, differentiated effector, and central memory CD8+ T cells during LCMV infection. Epigenomics-based annotation revealed a highly dynamic repertoire of enhancers, which were inherited, de novo activated, decommissioned and re-activated during CD8+ T cell responses. We employed a computational algorithm to pair enhancers with target gene promoters. On average, each enhancer targeted three promoters and each promoter was regulated by two enhancers. By identifying enriched transcription factor motifs in enhancers, we defined transcriptional regulatory circuitry at each CD8+ T cell response stage. These multi-dimensional datasets provide a blueprint for delineating molecular mechanisms underlying functional differentiation of CD8+ T cells.
AB - Differentiation of effector and memory CD8+ T cells is accompanied by extensive changes in the transcriptome and histone modifications at gene promoters; however, the enhancer repertoire and associated gene regulatory networks are poorly defined. Using histone mark chromatin immunoprecipitation coupled with deep sequencing, we mapped the enhancer and super-enhancer landscapes in antigen-specific naive, differentiated effector, and central memory CD8+ T cells during LCMV infection. Epigenomics-based annotation revealed a highly dynamic repertoire of enhancers, which were inherited, de novo activated, decommissioned and re-activated during CD8+ T cell responses. We employed a computational algorithm to pair enhancers with target gene promoters. On average, each enhancer targeted three promoters and each promoter was regulated by two enhancers. By identifying enriched transcription factor motifs in enhancers, we defined transcriptional regulatory circuitry at each CD8+ T cell response stage. These multi-dimensional datasets provide a blueprint for delineating molecular mechanisms underlying functional differentiation of CD8+ T cells.
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U2 - 10.1016/j.immuni.2016.11.009
DO - 10.1016/j.immuni.2016.11.009
M3 - Article
C2 - 27986453
AN - SCOPUS:85006701206
VL - 45
SP - 1341
EP - 1354
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 6
ER -