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Nat Immunol. 2016 Jun;17(6):695-703. doi: 10.1038/ni.3456. Epub 2016 Apr 25.

Tcf1 and Lef1 transcription factors establish CD8(+) T cell identity through intrinsic HDAC activity.

Author information

1
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
2
Department of Physics, The George Washington University, Washington, DC, USA.
3
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
4
Proteomics Facility, University of Iowa, Iowa City, Iowa, USA.
5
Interdisciplinary Immunology Graduate Program, University of Iowa, Iowa City, Iowa, USA.
6
Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
7
Transgenic Core Facility, NHLBI, National Institutes of Health, Bethesda, Maryland, USA.
8
Systems Biology Center, NHLBI, National Institutes of Health, Bethesda, Maryland, USA.
9
Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.

Abstract

The CD4(+) and CD8(+) T cell dichotomy is essential for effective cellular immunity. How individual T cell identity is established remains poorly understood. Here we show that the high-mobility group (HMG) transcription factors Tcf1 and Lef1 are essential for repressing CD4(+) lineage-associated genes including Cd4, Foxp3 and Rorc in CD8(+) T cells. Tcf1- and Lef1-deficient CD8(+) T cells exhibit histone hyperacetylation, which can be ascribed to intrinsic histone deacetylase (HDAC) activity in Tcf1 and Lef1. Mutation of five conserved amino acids in the Tcf1 HDAC domain diminishes HDAC activity and the ability to suppress CD4(+) lineage genes in CD8(+) T cells. These findings reveal that sequence-specific transcription factors can utilize intrinsic HDAC activity to guard cell identity by repressing lineage-inappropriate genes.

Comment in

PMID:
27111144
PMCID:
PMC4873337
DOI:
10.1038/ni.3456
[Indexed for MEDLINE]
Free PMC Article

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