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| Status |
Public on Mar 30, 2022 |
| Title |
The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes [ChIP-seq series 2] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Differentiation of progenitor cells into mature cell types is commonly associated with the expression of lineage-determining transcription factors (LD-TFs) specific to that lineage. In CD4+ T cells, T-bet dictates differentiation of the TH1 lineage, whereas GATA3 drives differentiation of the alternative TH2 lineage. LD-TFs, including T-bet and GATA3, are frequently co-expressed, both in vitro and in vivo. How co-expression of two mutually antagonistic LD-TFs affects their function and lineage determination is not known. By expressing T-bet and GATA3 separately or together, we show that T-bet sequesters GATA3 at its target sites, thereby removing GATA3 from TH2 genes. T-bet interacts with the GATA3 DNA binding domain, changing its DNA sequence binding preference. This mechanism allows T-bet to dominate and drive the TH1 gene expression program in the presence of the 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 TFs driving alternative differentiation pathways.
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| Overall design |
ChIP-seq for FLAG-T-bet and HA-GATA3 in EL4 cells expressing HA-GATA3 and Doxycycline-inducible T-bet. Cells were treated with a range of doxycycline (0-10ug/ml) for 48 hours prior to harvesting, to induce T-bet expression.
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| Contributor(s) |
Hertweck A, Jenner RG |
| Citation(s) |
35438764 |
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| Submission date |
Feb 10, 2022 |
| Last update date |
May 11, 2022 |
| Contact name |
Arnulf Hertweck |
| E-mail(s) |
a.hertweck@ucl.ac.uk
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| Organization name |
University College London
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| Department |
UCL Cancer Institute
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| Street address |
Gower Street
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| City |
London |
| ZIP/Postal code |
WC1E 6BT |
| Country |
United Kingdom |
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| Platforms (1) |
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| Samples (9)
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| GSM5885624 |
EL4_GATA3_Dox_Tbet_DOX_04_Flag-Tbet_ChIP |
| GSM5885625 |
EL4_GATA3_Dox_Tbet_DOX_10_Flag-Tbet_ChIP |
| GSM5885626 |
EL4_GATA3_Dox_Tbet_DOX_2_Flag-Tbet_ChIP |
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| This SubSeries is part of SuperSeries: |
| GSE171410 |
The TH1 cell lineage-determining transcription factor T-bet supresses TH2 gene expression by redistributing GATA3 away from TH2 genes |
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| Relations |
| BioProject |
PRJNA805234 |
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