Oct1 and OCA-B are selectively required for CD4 memory T cell function
Name
JEM_20150363.pdf
Size
3.11 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Shakya, Arvind
Goren, Alon
Shalek, Alex
German, Cody N.
Snook, Jeremy
Kuchroo, Vijay K.
Yosef, Nir
Chan, Raymond C.
Regev, Aviv
Williams, Matthew A.
Date Issued
October 2015
Journal
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Citation
Shakya, Arvind et al. “Oct1 and OCA-B Are Selectively Required for CD4 Memory T Cell Function.” The Journal of Experimental Medicine 212, 12 (October 2015): 2115–2131 © 2015 Shakya et al
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial share-alike 3.0 Unported
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DOI of Published Version
http://dx.doi.org/10.1084/JEM.20150363
