title: Bcl-6 directly represses the gene program of the glycolysis pathway.
abstract: Despite the increasing knowledge of the molecular events that induce the glycolysis pathway in effector T cells, very little is known about the transcriptional mechanisms that dampen the glycolysis program in quiescent cell populations such as memory T cells. Here we found that the transcription factor Bcl-6 directly repressed genes encoding molecules involved in the glycolysis pathway, including Slc2a1, Slc2a3, Pkm and Hk2, in type 1 helper T cells (TH1 cells) exposed to low concentrations of interleukin 2 (IL-2). Thus, Bcl-6 had a role opposing the IL-2-sensitive glycolytic transcriptional program that the transcription factors c-Myc and HIF-1α promote in effector T cells. Additionally, the TH1 lineage-specifying factor T-bet functionally antagonized the Bcl-6-dependent repression of genes encoding molecules in the glycolysis pathway, which links the molecular balance of these two factors to regulation of the metabolic gene program.
authors.affiliation: 1] Department of Immunology, University of Washington, Seattle, Washington, USA. [2] Virginia Tech Carilion Research Institute, Roanoke, Virginia, USA. [3] Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Oestreich
authors.affiliation: Virginia Tech Carilion Research Institute, Roanoke, Virginia, USA.
authors.forename: Kaitlin A
authors.initials: KA
authors.lastname: Read
authors.affiliation: Department of Immunology, University of Washington, Seattle, Washington, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gilbertson
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Hough
authors.affiliation: Virginia Tech Carilion Research Institute, Roanoke, Virginia, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: McDonald
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Krishnamoorthy
authors.affiliation: 1] Department of Immunology, University of Washington, Seattle, Washington, USA. [2] Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Weinmann
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006019:Glycolysis / Q000235:genetics*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051560:Proto-Oncogene Proteins c-bcl-6; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007376:Interleukin-2; D051560:Proto-Oncogene Proteins c-bcl-6