Epigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation.
Bingfei YuKai ZhangJ Justin MilnerClara TomaRunqiang ChenJames P Scott-BrowneRenata M PereiraShane CrottyJohn T ChangMatthew E PipkinWei WangAnanda W GoldrathPublished in: Nature immunology (2017)
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.
Keyphrases
- genome wide
- dna methylation
- gene expression
- transcription factor
- single cell
- poor prognosis
- working memory
- regulatory t cells
- dendritic cells
- binding protein
- electronic health record
- cell therapy
- big data
- type iii
- machine learning
- copy number
- minimally invasive
- deep learning
- stem cells
- immune response
- diabetic rats
- hiv infected
- cell proliferation
- cell cycle arrest
- endothelial cells
- stress induced