期刊
NATURE IMMUNOLOGY
卷 18, 期 5, 页码 573-582出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3706
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资金
- University of California, San Diego
- US National Institutes of Health [A1067545, A1072117, U19AI109976, U54HG006997, AR070310, R01 AI109842, AI40127]
- Leukemia and Lymphoma Society
- Pew Scholars Fund
- Pew Latin American Fellows Program in the Biomedical Sciences
- Damon Runyon Cancer Research Foundation
Dynamic changes in the expression of transcription factors (TFs) can influence the specification of distinct CD8(+) T cell fates, but the observation of equivalent expression of TFs among differentially fated precursor cells suggests additional underlying mechanisms. Here we profiled the genome-wide histone modifications, open chromatin and gene expression of naive, terminal-effector, memory-precursor and memory CD8(+) T cell populations induced during the in vivo response to bacterial infection. Integration of these data suggested that the expression and binding of TFs contributed to the establishment of subset-specific enhancers during differentiation. We developed a new bioinformatics method using the PageRank algorithm to reveal key TFs that influence the generation of effector and memory populations. The TFs YY1 and Nr3c1, both constitutively expressed during CD8(+) T cell differentiation, regulated the formation of terminal-effector cell fates and memory-precursor cell fates, respectively. Our data define the epigenetic landscape of differentiation intermediates and facilitate the identification of TFs with previously unappreciated roles in CD8(+) T cell differentiation.
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