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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Alternative title
A genome-wide regulatory network identifies key transcription factors for memory CD8+ T-cell development
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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
2013-12Department
Massachusetts Institute of Technology. Department of Biology; Koch Institute for Integrative Cancer Research at MITJournal
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