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Epigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation.


ABSTRACT: 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.

SUBMITTER: Yu B 

PROVIDER: S-EPMC5395420 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Epigenetic landscapes reveal transcription factors that regulate CD8<sup>+</sup> T cell differentiation.

Yu Bingfei B   Zhang Kai K   Milner J Justin JJ   Toma Clara C   Chen Runqiang R   Scott-Browne James P JP   Pereira Renata M RM   Crotty Shane S   Chang John T JT   Pipkin Matthew E ME   Wang Wei W   Goldrath Ananda W AW  

Nature immunology 20170313 5


Dynamic changes in the expression of transcription factors (TFs) can influence the specification of distinct CD8<sup>+</sup> 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<sup>+</sup> T cell populations induced during the in vivo response to b  ...[more]

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