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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-1? 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.

SUBMITTER: Oestreich KJ

PROVIDER: S-EPMC4226759 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Bcl-6 directly represses the gene program of the glycolysis pathway.

Oestreich Kenneth J KJ Read Kaitlin A KA Gilbertson Sarah E SE Hough Kenneth P KP McDonald Paul W PW Krishnamoorthy Veena V Weinmann Amy S AS

Nature immunology 20140907 10

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 i ...[more]

PMID: 25194422

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