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

• Main Authors: Hu, Guangan (Contributor), Chen, Jianzhu (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor)
• Format: Article
• Language: English
• Published: Nature Publishing Group, 2014-07-01T14:37:15Z.
• Subjects: Article
• Online Access: Get fulltext

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)