학술논문
The TH1 cell lineage-determining transcription factor T-bet suppresses TH2 gene expression by redistributing GATA3 away from TH2 genes.
Document Type
Academic Journal
Author
Hertweck A; UCL Cancer Institute and Cancer Research UK UCL Centre, University College London (UCL), London, WC1E 6BT, UK.; Vila de Mucha M; UCL Cancer Institute and Cancer Research UK UCL Centre, University College London (UCL), London, WC1E 6BT, UK.; Barber PR; UCL Cancer Institute and Cancer Research UK UCL Centre, University College London (UCL), London, WC1E 6BT, UK.; Comprehensive Cancer Centre, School of Cancer & Pharmaceutical Sciences, King's College London, London, SE1 1UL, UK.; Dagil R; Research Department of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London, WC1E 6XA, UK.; Porter H; UCL Cancer Institute and Cancer Research UK UCL Centre, University College London (UCL), London, WC1E 6BT, UK.; Ramos A; Research Department of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London, WC1E 6XA, UK.; Lord GM; Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9NT, UK.; Jenner RG; UCL Cancer Institute and Cancer Research UK UCL Centre, University College London (UCL), London, WC1E 6BT, UK.
Source
Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
Subject
Language
English
Abstract
Lineage-determining transcription factors (LD-TFs) drive the differentiation of progenitor cells into a specific lineage. In CD4+ T cells, T-bet dictates differentiation of the TH1 lineage, whereas GATA3 drives differentiation of the alternative TH2 lineage. However, LD-TFs, including T-bet and GATA3, are frequently co-expressed but how this affects LD-TF function is not known. By expressing T-bet and GATA3 separately or together in mouse T cells, we show that T-bet sequesters GATA3 at its target sites, thereby removing GATA3 from TH2 genes. This redistribution of GATA3 is independent of GATA3 DNA binding activity and is instead mediated by the T-bet DNA binding domain, which interacts with the GATA3 DNA binding domain and changes GATA3's sequence binding preference. This mechanism allows T-bet to drive the TH1 gene expression program in the presence of GATA3. We propose that redistribution of one LD-TF by another may be a common mechanism that could explain how specific cell fate choices can be made even in the presence of other transcription factors driving alternative differentiation pathways.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
(© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)