Format

Send to

Choose Destination
Nat Immunol. 2017 May;18(5):573-582. doi: 10.1038/ni.3706. Epub 2017 Mar 13.

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

Author information

1
Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
2
Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, California, USA.
3
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
4
Department of Immunology and Microbial Science, The Scripps Research Institute, Jupiter, Florida, USA.
5
Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
6
Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
7
Department of Medicine, University of California, San Diego, La Jolla, California, USA.
8
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, USA.
9
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, USA.

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.

PMID:
28288100
PMCID:
PMC5395420
DOI:
10.1038/ni.3706
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center