A genome-wide regulatory network identifies key transcription factors for memory CD8[superscript +] T-cell development
Memory CD8[superscript +] T-cell development is defined by the expression of a specific set of memory signature genes. Despite recent progress, many components of the transcriptional control of memory CD8[superscript +] T-cell development are still unknown. To identify transcription factors and thei...
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Nature Publishing Group
2014
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Online Access: | http://hdl.handle.net/1721.1/88162 https://orcid.org/0000-0003-1828-0509 https://orcid.org/0000-0002-5687-6154 |
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author | Hu, Guangan Chen, Jianzhu |
author2 | Massachusetts Institute of Technology. Department of Biology |
author_facet | Massachusetts Institute of Technology. Department of Biology Hu, Guangan Chen, Jianzhu |
author_sort | Hu, Guangan |
collection | MIT |
description | Memory CD8[superscript +] T-cell development is defined by the expression of a specific set of memory signature genes. Despite recent progress, many components of the transcriptional control of memory CD8[superscript +] T-cell development are still unknown. To identify transcription factors and their interactions in memory CD8[superscript +] T-cell development, we construct a genome-wide regulatory network and apply it to identify key transcription factors that regulate memory signature genes. Most of the known transcription factors having a role in memory CD8[superscript +] T-cell development are rediscovered and about a dozen new ones are also identified. Sox4, Bhlhe40, Bach2 and Runx2 are experimentally verified, and Bach2 is further shown to promote both development and recall proliferation of memory CD8[superscript +] T cells through Prdm1 and Id3. Gene perturbation study identifies the interactions between the transcription factors, with Sox4 positioned as a hub. The identified transcription factors and insights into their interactions should facilitate further dissection of molecular mechanisms underlying memory CD8[superscript +] T-cell development. |
first_indexed | 2024-09-23T16:59:51Z |
format | Article |
id | mit-1721.1/88162 |
institution | Massachusetts Institute of Technology |
language | en_US |
last_indexed | 2024-09-23T16:59:51Z |
publishDate | 2014 |
publisher | Nature Publishing Group |
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spelling | mit-1721.1/881622022-10-03T09:38:37Z A genome-wide regulatory network identifies key transcription factors for memory CD8[superscript +] T-cell development A genome-wide regulatory network identifies key transcription factors for memory CD8+ T-cell development Hu, Guangan Chen, Jianzhu Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Chen, Jianzhu Hu, Guangan Chen, Jianzhu Memory CD8[superscript +] T-cell development is defined by the expression of a specific set of memory signature genes. Despite recent progress, many components of the transcriptional control of memory CD8[superscript +] T-cell development are still unknown. To identify transcription factors and their interactions in memory CD8[superscript +] T-cell development, we construct a genome-wide regulatory network and apply it to identify key transcription factors that regulate memory signature genes. Most of the known transcription factors having a role in memory CD8[superscript +] T-cell development are rediscovered and about a dozen new ones are also identified. Sox4, Bhlhe40, Bach2 and Runx2 are experimentally verified, and Bach2 is further shown to promote both development and recall proliferation of memory CD8[superscript +] T cells through Prdm1 and Id3. Gene perturbation study identifies the interactions between the transcription factors, with Sox4 positioned as a hub. The identified transcription factors and insights into their interactions should facilitate further dissection of molecular mechanisms underlying memory CD8[superscript +] T-cell development. Singapore-MIT Alliance National Institutes of Health (U.S.) (Grant AI69208) National Cancer Institute (U.S.) (Koch Institute Support (core) Grant P30-CA14051) 2014-07-01T14:37:15Z 2014-07-01T14:37:15Z 2013-12 2013-06 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/88162 Hu, Guangan, and Jianzhu Chen. “A Genome-Wide Regulatory Network Identifies Key Transcription Factors for Memory CD8[superscript +] T-Cell Development.” Nature Communications 4 (December 12, 2013). https://orcid.org/0000-0003-1828-0509 https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.1038/ncomms3830 Nature Communications Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group Chen |
spellingShingle | Hu, Guangan Chen, Jianzhu A genome-wide regulatory network identifies key transcription factors for memory CD8[superscript +] T-cell development |
title | A genome-wide regulatory network identifies key transcription factors for memory CD8[superscript +] T-cell development |
title_full | A genome-wide regulatory network identifies key transcription factors for memory CD8[superscript +] T-cell development |
title_fullStr | A genome-wide regulatory network identifies key transcription factors for memory CD8[superscript +] T-cell development |
title_full_unstemmed | A genome-wide regulatory network identifies key transcription factors for memory CD8[superscript +] T-cell development |
title_short | A genome-wide regulatory network identifies key transcription factors for memory CD8[superscript +] T-cell development |
title_sort | genome wide regulatory network identifies key transcription factors for memory cd8 superscript t cell development |
url | http://hdl.handle.net/1721.1/88162 https://orcid.org/0000-0003-1828-0509 https://orcid.org/0000-0002-5687-6154 |
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