title: 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.
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Bingfei
authors.initials: B
authors.lastname: Yu
authors.affiliation: Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, California, USA.
authors.forename: Kai
authors.identifier: 0000-0003-3454-7357
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: J Justin
authors.initials: JJ
authors.lastname: Milner
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Clara
authors.initials: C
authors.lastname: Toma
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.|Department of Immunology and Microbial Science, The Scripps Research Institute, Jupiter, Florida, USA.
authors.forename: Runqiang
authors.initials: R
authors.lastname: Chen
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Scott-Browne
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Renata M
authors.initials: RM
authors.lastname: Pereira
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.|Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: Shane
authors.identifier: 0000-0002-6484-6262
authors.initials: S
authors.lastname: Crotty
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Chang
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, Jupiter, Florida, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Pipkin
authors.affiliation: Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, California, USA.|Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, USA.|Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Ananda W
authors.initials: AW
authors.lastname: Goldrath
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000382:microbiology / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D019295:Computational Biology; D004742:Enhancer Elements, Genetic / Q000235:genetics; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism; D007156:Immunologic Memory / Q000235:genetics; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000382:microbiology / Q000502:physiology*; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; C575863:NR3C1 protein, mouse; D011965:Receptors, Glucocorticoid; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse