title: A genome-wide regulatory network identifies key transcription factors for memory CD8⁺ T-cell development.
abstract: 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.
authors: David H. Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors: Guangan
authors: G
authors: Hu
authors: David H. Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors: Jianzhu
authors: J
authors: Chen
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D004285:Dogs; D053263:Gene Regulatory Networks / Q000276:immunology*; D055106:Genome-Wide Association Study; D007156:Immunologic Memory / Q000235:genetics*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055751:SOXC Transcription Factors / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C102109:Bach2 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D055751:SOXC Transcription Factors; C489990:Sox4 protein, mouse; D014157:Transcription Factors