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T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements

Author

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  • Aditi Kanhere

    (University College London
    Present address: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK)

  • Arnulf Hertweck

    (Guy’s and St Thomas’ Hospital and King’s College London)

  • Urvashi Bhatia

    (Guy’s and St Thomas’ Hospital and King’s College London)

  • M. Refik Gökmen

    (Guy’s and St Thomas’ Hospital and King’s College London)

  • Esperanza Perucha

    (Guy’s and St Thomas’ Hospital and King’s College London)

  • Ian Jackson

    (Guy’s and St Thomas’ Hospital and King’s College London)

  • Graham M. Lord

    (Guy’s and St Thomas’ Hospital and King’s College London)

  • Richard G. Jenner

    (University College London)

Abstract

T-bet and GATA3 regulate the CD4+ T cell Th1/Th2 cell fate decision but little is known about the interplay between these factors outside of the murine Ifng and Il4/Il5/Il13 loci. Here we show that T-bet and GATA3 bind to multiple distal sites at immune regulatory genes in human effector T cells. These sites display markers of functional elements, act as enhancers in reporter assays and are associated with a requirement for T-bet and GATA3. Furthermore, we demonstrate that both factors bind distal sites at Tbx21 and that T-bet directly activates its own expression. We also show that in Th1 cells, GATA3 is distributed away from Th2 genes, instead occupying T-bet binding sites at Th1 genes, and that T-bet is sufficient to induce GATA3 binding at these sites. We propose these aspects of T-bet and GATA3 function are important for Th1/Th2 differentiation and for understanding transcription factor interactions in other T cell lineage decisions.

Suggested Citation

  • Aditi Kanhere & Arnulf Hertweck & Urvashi Bhatia & M. Refik Gökmen & Esperanza Perucha & Ian Jackson & Graham M. Lord & Richard G. Jenner, 2012. "T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2260
    DOI: 10.1038/ncomms2260
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    Cited by:

    1. Changxu Fan & Xiaoyun Xing & Samuel J. H. Murphy & Jennifer Poursine-Laurent & Heather Schmidt & Bijal A. Parikh & Jeesang Yoon & Mayank N. K. Choudhary & Naresha Saligrama & Sytse J. Piersma & Wayne , 2024. "Cis-regulatory evolution of the recently expanded Ly49 gene family," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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