Format

Send to

Choose Destination
Immunity. 2017 Aug 15;47(2):251-267.e7. doi: 10.1016/j.immuni.2017.07.015.

CCCTC-Binding Factor Translates Interleukin 2- and α-Ketoglutarate-Sensitive Metabolic Changes in T Cells into Context-Dependent Gene Programs.

Author information

1
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
2
HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
3
Department of Molecular Biology, University of California San Diego, La Jolla, CA 92093, USA.
4
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
5
Heflin Center for Genomic Science, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
6
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: weinmann@uab.edu.

Abstract

Despite considerable research connecting cellular metabolism with differentiation decisions, the underlying mechanisms that translate metabolite-sensitive activities into unique gene programs are still unclear. We found that aspects of the interleukin-2 (IL-2)-sensitive effector gene program in CD4+ and CD8+ T cells in type 1 conditions (Th1) were regulated by glutamine and alpha-ketoglutarate (αKG)-induced events, in part through changes in DNA and histone methylation states. We further identified a mechanism by which IL-2- and αKG-sensitive metabolic changes regulated the association of CCCTC-binding factor (CTCF) with select genomic sites. αKG-sensitive CTCF sites were often associated with loci containing IL-2- and αKG-sensitive genome organization patterns and gene expression in T cells. IL-2- and αKG-sensitive CTCF sites in T cells were also associated with genes from developmental pathways that had αKG-sensitive expression in embryonic stem cells. The data collectively support a mechanism wherein CTCF serves to translate αKG-sensitive metabolic changes into context-dependent differentiation gene programs.

PMID:
28813658
PMCID:
PMC5654635
DOI:
10.1016/j.immuni.2017.07.015
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center