The TH1 cell lineage-determining transcription factor T-bet suppresses TH2 gene expression by redistributing GATA3 away from TH2 genes

Research output: Contribution to journalJournal articleResearchpeer-review

  • Arnulf Hertweck
  • Maria Vila de Mucha
  • Paul R Barber
  • Dagil, Robert
  • Hayley Porter
  • Andres Ramos
  • Graham M Lord
  • Richard G Jenner

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.

Original languageEnglish
JournalNucleic Acids Research
Volume50
Issue number8
Pages (from-to)4557–4573
ISSN0305-1048
DOIs
Publication statusPublished - 2022
Externally publishedYes

Bibliographical note

© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

ID: 303686976