%0 Journal Article
%A Delacher, Michael
%A Barra, Melanie M
%A Herzig, Yonatan
%A Eichelbaum, Katrin
%A Rafiee, Mahmoud-Reza
%A Richards, David M
%A Träger, Ulrike
%A Hofer, Ann-Cathrin
%A Kazakov, Alexander
%A Braband, Kathrin
%A Gonzalez, Marina
%A Wöhrl, Lukas
%A Schambeck, Kathrin
%A Imbusch, Charles D
%A Abramson, Jakub
%A Krijgsveld, Jeroen
%A Feuerer, Markus
%T Quantitative Proteomics Identifies TCF1 as a Negative Regulator of Foxp3 Expression in Conventional T Cells.
%J iScience
%V 23
%N 5
%@ 2589-0042
%C St. Louis
%I Elsevier
%M DKFZ-2020-01311
%P 101127
%D 2020
%Z #EA:D100#LA:D100#
%X Regulatory T cells are important regulators of the immune system and have versatile functions for the homeostasis and repair of tissues. They express the forkhead box transcription factor Foxp3 as a lineage-defining protein. Negative regulators of Foxp3 expression are not well understood. Here, we generated double-stranded DNA probes complementary to the Foxp3 promoter sequence and performed a pull-down with nuclear protein in vitro, followed by elution of bound proteins and quantitative mass spectrometry. Of the Foxp3-promoter-binding transcription factors identified with this approach, one was T cell factor 1 (TCF1). Using viral over-expression, we identified TCF1 as a repressor of Foxp3 expression. In TCF1-deficient animals, increased levels of Foxp3intermediateCD25negative T cells were identified. CRISPR-Cas9 knockout studies in primary human and mouse conventional CD4 T (Tconv) cells revealed that TCF1 protects Tconv cells from inadvertent Foxp3 expression. Our data implicate a role of TCF1 in suppressing Foxp3 expression in activated T cells.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:32422593
%2 pmc:PMC7229326
%R 10.1016/j.isci.2020.101127
%U https://inrepo02.dkfz.de/record/157014