Journal article
CD8+ T Cells Utilize Highly Dynamic Enhancer Repertoires and Regulatory Circuitry in Response to Infections
Immunity (Cambridge, Mass.), Vol.45(6), pp.1341-1354
12/20/2016
DOI: 10.1016/j.immuni.2016.11.009
PMID: 27986453
Abstract
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.
•Comprehensive epigenomic mapping in naive, effector, and memory CD8+ T cells•Enhancers and super enhancers are dynamically regulated during CD8+ T cell responses•Re-wiring of regulatory circuitry mediated by dynamic enhancer-promoter interactome•Network analysis identifies novel regulators during CD8+ T cell response stages
He et al. performed comprehensive epigenomic profiling and mapped a highly dynamic repertoire of active enhancers and super enhancers during CD8+ T cell responses to infection. Integrative analyses revealed extensive re-wiring of regulatory circuits and identified key regulators during the transition from naïve to effector and memory CD8+ T cells.
Details
- Title: Subtitle
- CD8+ T Cells Utilize Highly Dynamic Enhancer Repertoires and Regulatory Circuitry in Response to Infections
- Creators
- Bing He - Division of Oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USAShaojun Xing - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAChangya Chen - Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242, USAPeng Gao - Division of Oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USALi Teng - Illumina Inc., San Diego, CA 92122, USAQiang Shan - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAJodi A Gullicksrud - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAMatthew D Martin - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAShuyang Yu - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, P.R. China 100193John T Harty - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAVladimir P Badovinac - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAKai Tan - Division of Oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USAHai-Hui Xue - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Immunity (Cambridge, Mass.), Vol.45(6), pp.1341-1354
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.immuni.2016.11.009
- PMID
- 27986453
- ISSN
- 1074-7613
- eISSN
- 1097-4180
- Language
- English
- Date published
- 12/20/2016
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984047744302771
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