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...

Full description

Bibliographic Details
Main Authors: Hu, Guangan, Chen, Jianzhu
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Nature Publishing Group 2014
Online Access:http://hdl.handle.net/1721.1/88162
https://orcid.org/0000-0003-1828-0509
https://orcid.org/0000-0002-5687-6154
_version_ 1811097458295439360
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
record_format dspace
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
work_keys_str_mv AT huguangan agenomewideregulatorynetworkidentifieskeytranscriptionfactorsformemorycd8superscripttcelldevelopment
AT chenjianzhu agenomewideregulatorynetworkidentifieskeytranscriptionfactorsformemorycd8superscripttcelldevelopment
AT huguangan agenomewideregulatorynetworkidentifieskeytranscriptionfactorsformemorycd8tcelldevelopment
AT chenjianzhu agenomewideregulatorynetworkidentifieskeytranscriptionfactorsformemorycd8tcelldevelopment
AT huguangan genomewideregulatorynetworkidentifieskeytranscriptionfactorsformemorycd8superscripttcelldevelopment
AT chenjianzhu genomewideregulatorynetworkidentifieskeytranscriptionfactorsformemorycd8superscripttcelldevelopment