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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647264/ https://www.ncbi.nlm.nih.gov/pubmed/26481684 http://dx.doi.org/10.1084/jem.20150363 |
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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 |
author_facet | 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 | PubMed |
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. |
format | Online Article Text |
id | pubmed-4647264 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-46472642016-05-16 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 J Exp Med Research Articles 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. The Rockefeller University Press 2015-11-16 /pmc/articles/PMC4647264/ /pubmed/26481684 http://dx.doi.org/10.1084/jem.20150363 Text en © 2015 Shakya et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles 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 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647264/ https://www.ncbi.nlm.nih.gov/pubmed/26481684 http://dx.doi.org/10.1084/jem.20150363 |
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