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

Shaojun Xing; Fengyin Li; Zhouhao Zeng; Yunjie Zhao; Shuyang Yu; Qiang Shan; Yalan Li; Farrah C Phillips; Peterson K Maina; Hank H Qi; Chengyu Liu; Jun Zhu; R Marshall Pope; Catherine A Musselman; Chen Zeng; Weiqun Peng; Hai-Hui Xue

doi:10.1038/ni.3456

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

Journal article

Peer reviewed

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

Shaojun Xing, Fengyin Li, Zhouhao Zeng, Yunjie Zhao, Shuyang Yu, Qiang Shan, Yalan Li, Farrah C Phillips, Peterson K Maina, Hank H Qi, …

Nature immunology, Vol.17(6), pp.695-703

06/01/2016

DOI: 10.1038/ni.3456

PMCID: PMC4873337

PMID: 27111144

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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.

Acetylation

Animals

CD4-Positive T-Lymphocytes - immunology

CD8-Positive T-Lymphocytes - immunology

Cell Differentiation - genetics

Cell Lineage - genetics

Cells, Cultured

Female

Gene Expression Regulation

Hepatocyte Nuclear Factor 1-alpha - genetics

Hepatocyte Nuclear Factor 1-alpha - metabolism

Histone Deacetylases - genetics

Histone Deacetylases - metabolism

Lymphoid Enhancer-Binding Factor 1 - genetics

Lymphoid Enhancer-Binding Factor 1 - metabolism

Male

Mice

Mice, Inbred C57BL

Mice, Knockout

Mutation - genetics

Protein Domains - genetics

Details

Title: Subtitle: Tcf1 and Lef1 transcription factors establish CD8(+) T cell identity through intrinsic HDAC activity
Creators: Shaojun Xing - University of Iowa
Fengyin Li - University of Iowa
Zhouhao Zeng - George Washington University
Yunjie Zhao - George Washington University
Shuyang Yu - China Agricultural University
Qiang Shan - University of Iowa
Yalan Li - University of Iowa
Farrah C Phillips - University of Iowa
Peterson K Maina - University of Iowa
Hank H Qi - University of Iowa
Chengyu Liu - National Heart Lung and Blood Institute
Jun Zhu - National Institutes of Health
R Marshall Pope - University of Iowa
Catherine A Musselman - University of Iowa
Chen Zeng - George Washington University
Weiqun Peng - George Washington University
Hai-Hui Xue - University of Iowa
Resource Type: Journal article
Publication Details: Nature immunology, Vol.17(6), pp.695-703
DOI: 10.1038/ni.3456
PMID: 27111144
PMCID: PMC4873337
ISSN: 1529-2908
eISSN: 1529-2916
Grant note: R01 AI112579 / NIAID NIH HHS I01 BX002903 / BLRD VA R21 AI105351 / NIAID NIH HHS R21 AI119160 / NIAID NIH HHS R21 AI115149 / NIAID NIH HHS S10 OD016199 / NIH HHS P30 CA086862 / NCI NIH HHS R21 AI113806 / NIAID NIH HHS
Language: English
Date published: 06/01/2016
Academic Unit: Medicine Administration
Record Identifier: 9984627221802771

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