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Tcf1 and Lef1 establish CD8+ T cell identity via their intrinsic histone deacetylase activity

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE73240 | GEO | 2016/02/12

SECONDARY ACCESSION(S): PRJNA296431

REPOSITORIES: GEO

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Tcf1 and Lef1 establish CD8+ T cell identity via their intrinsic histone deacetylase activity

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-02-12 | E-GEOD-73240 | biostudies-arrayexpress

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

Project description: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.

| S-EPMC4873337 | biostudies-literature

Tcf1 and Lef1 establish CD8+ T cell identity via their intrinsic histone deacetylase activity

Project description:Tcf1 and Lef1 establish CD8+ T cell identity via their intrinsic histone deacetylase activity

| PRJNA296431 | ENA

Tcf1 and Lef1 provide constant supervision to mature CD8<sup>+</sup> T cell identity and function by organizing genomic architecture.

Project description:T cell identity is established during thymic development, but how it is maintained in the periphery remains unknown. Here we show that ablating Tcf1 and Lef1 transcription factors in mature CD8+ T cells aberrantly induces genes from non-T cell lineages. Using high-throughput chromosome-conformation-capture sequencing, we demonstrate that Tcf1/Lef1 are important for maintaining three-dimensional genome organization at multiple scales in CD8+ T cells. Comprehensive network analyses coupled with genome-wide profiling of chromatin accessibility and Tcf1 occupancy show the direct impact of Tcf1/Lef1 on the T cell genome is to promote formation of extensively interconnected hubs through enforcing chromatin interaction and accessibility. The integrative mechanisms utilized by Tcf1/Lef1 underlie activation of T cell identity genes and repression of non-T lineage genes, conferring fine control of various T cell functionalities. These findings suggest that Tcf1/Lef1 control global genome organization and help form intricate chromatin-interacting hubs to facilitate promoter-enhancer/silencer contact, hence providing constant supervision of CD8+ T cell identity and function.

| S-EPMC8494933 | biostudies-literature

Tcf1/Lef1 transcription factors and CD8 T cell identity

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-07-11 | GSE164713 | GEO

TCF1 and LEF1 act as T-cell intrinsic HTLV-1 antagonists by targeting Tax.

Project description:Human T-cell leukemia virus type 1 (HTLV-1) is a delta-type retrovirus that induces malignant and inflammatory diseases during its long persistence in vivo. HTLV-1 can infect various kinds of cells; however, HTLV-1 provirus is predominantly found in peripheral CD4 T cells in vivo. Here we find that TCF1 and LEF1, two Wnt transcription factors that are specifically expressed in T cells, inhibit viral replication through antagonizing Tax functions. TCF1 and LEF1 can each interact with Tax and inhibit Tax-dependent viral expression and activation of NF-?B and AP-1. As a result, HTLV-1 replication is suppressed in the presence of either TCF1 or LEF1. On the other hand, T-cell activation suppresses the expression of both TCF1 and LEF1, and this suppression enables Tax to function as an activator. We analyzed the thymus of a simian T-cell leukemia virus type 1 (STLV-1) infected Japanese macaque, and found a negative correlation between proviral load and TCF1/LEF1 expression in various T-cell subsets, supporting the idea that TCF1 and LEF1 negatively regulate HTLV-1 replication and the proliferation of infected cells. Thus, this study identified TCF1 and LEF1 as Tax antagonistic factors in vivo, a fact which may critically influence the peripheral T-cell tropism of this virus.

| S-EPMC4343127 | biostudies-other

Tcf1/Lef1 transcription factors and CD8 T cell identity [DNAase-seq]

Project description:Comparison of chromatin accessibility profiles between WT and Tcf1/Lef1-deficient naïve CD8+ T cells

2021-07-11 | GSE164689 | GEO

Tcf1/Lef1 transcription factors and CD8 T cell identity [RNA-seq]

Project description:Comparison of transcriptomes between WT and Tcf1/Lef1-deficient naïve CD8+ T cells

2021-07-11 | GSE164712 | GEO