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 facto...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
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Rockefeller University Press
2018
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| Online Access: | http://hdl.handle.net/1721.1/113558 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1811068532048265216 |
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| author | Shakya, Arvind Goren, Alon Shalek, Alex German, Cody N. Snook, Jeremy Kuchroo, Vijay K. Yosef, Nir Chan, Raymond C. Regev, Aviv Williams, Matthew A. Tantin, Dean |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Shakya, Arvind Goren, Alon Shalek, Alex German, Cody N. Snook, Jeremy Kuchroo, Vijay K. Yosef, Nir Chan, Raymond C. Regev, Aviv Williams, Matthew A. Tantin, Dean |
| author_sort | Shakya, Arvind |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T07:57:22Z |
| format | Article |
| id | mit-1721.1/113558 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T07:57:22Z |
| publishDate | 2018 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | mit-1721.1/1135582022-09-23T09:53:27Z Oct1 and OCA-B are selectively required for CD4 memory T cell function Shakya, Arvind Goren, Alon Shalek, Alex German, Cody N. Snook, Jeremy Kuchroo, Vijay K. Yosef, Nir Chan, Raymond C. Regev, Aviv Williams, Matthew A. Tantin, Dean Massachusetts Institute of Technology. Department of Biology Regev, Aviv 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. 2018-02-09T16:43:22Z 2018-02-09T16:43:22Z 2015-10 2015-02 2018-02-05T19:03:32Z Article http://purl.org/eprint/type/JournalArticle 0022-1007 1540-9538 http://hdl.handle.net/1721.1/113558 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 https://orcid.org/0000-0001-8567-2049 http://dx.doi.org/10.1084/JEM.20150363 The Journal of Experimental Medicine Creative Commons Attribution-NonCommercial share-alike 3.0 Unported http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Rockefeller University Press Rockefeller University Press |
| spellingShingle | Shakya, Arvind Goren, Alon Shalek, Alex German, Cody N. Snook, Jeremy Kuchroo, Vijay K. Yosef, Nir Chan, Raymond C. Regev, Aviv Williams, Matthew A. Tantin, Dean Oct1 and OCA-B are selectively required for CD4 memory T cell function |
| title | Oct1 and OCA-B are selectively required for CD4 memory T cell function |
| title_full | Oct1 and OCA-B are selectively required for CD4 memory T cell function |
| title_fullStr | Oct1 and OCA-B are selectively required for CD4 memory T cell function |
| title_full_unstemmed | Oct1 and OCA-B are selectively required for CD4 memory T cell function |
| title_short | Oct1 and OCA-B are selectively required for CD4 memory T cell function |
| title_sort | oct1 and oca b are selectively required for cd4 memory t cell function |
| url | http://hdl.handle.net/1721.1/113558 https://orcid.org/0000-0001-8567-2049 |
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