Oct1 and OCA-B are selectively required for CD4 memory T cell function.
Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4(+) memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4(+) T cells. OCA-B is also required for the robust reexpression of multiple other genes including Ifng. ChIPseq identifies ∼50 differentially expressed direct Oct1 and OCA-B targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2, Ifng, and Zbtb32. The findings pinpoint Oct1 and OCA-B as central mediators of CD4(+) T cell memory.
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112.
Arvind
A
Shakya
Broad Technology Labs, The Broad Institute of MIT and Harvard, Cambridge, MA 02142.
Alon
A
Goren
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138 Department of Physics, Harvard University, Cambridge, MA 02138 The Broad Institute of MIT and Harvard, Cambridge, MA 02142​
Alex
A
Shalek
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112.
Cody N
CN
German
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112.
Jeremy
J
Snook
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 The Broad Institute of MIT and Harvard, Cambridge, MA 02142​
Vijay K
VK
Kuchroo
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 The Broad Institute of MIT and Harvard, Cambridge, MA 02142​
Nir
N
Yosef
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109.
Raymond C
RC
Chan
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139 The Broad Institute of MIT and Harvard, Cambridge, MA 02142​
Aviv
A
Regev
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112 dean.tantin@path.utah.edu matthew.williams@path.utah.edu.
Matthew A
MA
Williams
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112 dean.tantin@path.utah.edu matthew.williams@path.utah.edu.
Dean
D
Tantin
D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050811:Octamer Transcription Factor-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D007376:Interleukin-2; D050811:Octamer Transcription Factor-1; C490424:Pou2af1 protein, mouse; D012097:Repressor Proteins; C406863:Rog protein, mouse; D015534:Trans-Activators; D007371:Interferon-gamma; D056484:Jumonji Domain-Containing Histone Demethylases; C511045:Kdm3a protein, mouse