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A genome-wide regulatory network identifies key transcription factors for memory CD8[superscript +] T-cell development

Author(s)
Hu, Guangan; Chen, Jianzhu
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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.

Alternative title
A genome-wide regulatory network identifies key transcription factors for memory CD8+ T-cell development
Terms of use
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.
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Abstract
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.
Date issued
2013-12
URI
http://hdl.handle.net/1721.1/88162
Department
Massachusetts Institute of Technology. Department of Biology; Koch Institute for Integrative Cancer Research at MIT
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
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).
Version: Author's final manuscript
ISSN
2041-1723

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