Journal
NATURE COMMUNICATIONS
Volume 4, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms3830
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Funding
- National Institutes of Health [AI69208]
- Singapore-MIT Alliance
- Ivan R. Cottrell Professorship and Research Fund
- National Cancer Institute [P30-CA14051]
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Memory CD8(+) 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(+) T-cell development are still unknown. To identify transcription factors and their interactions in memory CD8(+) 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(+) 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(+) 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(+) T-cell development.
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