Imperial College London
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DrMasahiroOno

Faculty of Natural Sciences, Department of Life Sciences

Reader in Immunology
 
 
 
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Contact

 

m.ono

 
 
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Location

 

605Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lau:2021:10.1242/dev.199754,
author = {Lau, C-I and Rowell, J and Yanez, DC and Solanki, A and Ross, S and Ono, M and Crompton, T},
doi = {10.1242/dev.199754},
journal = {Development},
title = {The pioneer transcription factors Foxa1 and Foxa2 regulate alternative RNA splicing during thymocyte positive selection.},
url = {http://dx.doi.org/10.1242/dev.199754},
volume = {148},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - During positive selection at the transition from CD4+CD8+ double-positive (DP) to single-positive (SP) thymocyte, TCR signalling results in appropriate MHC restriction and signals for survival and progression. We show that the pioneer transcription factors Foxa1 and Foxa2 are required to regulate RNA splicing during positive selection of mouse T cells and that Foxa1 and Foxa2 have overlapping/compensatory roles. Conditional deletion of both Foxa1 and Foxa2 from DP thymocytes reduced positive selection and development of CD4SP, CD8SP and peripheral naïve CD4+ T cells. Foxa1 and Foxa2 regulated the expression of many genes encoding splicing factors and regulators, including Mbnl1, H1f0, Sf3b1, Hnrnpa1, Rnpc3, Prpf4b, Prpf40b and Snrpd3. Within the positively selecting CD69+DP cells, alternative RNA splicing was dysregulated in the double Foxa1/Foxa2 conditional knockout, leading to >850 differentially used exons. Many genes important for this stage of T-cell development (Ikzf1-3, Ptprc, Stat5a, Stat5b, Cd28, Tcf7) and splicing factors (Hnrnpab, Hnrnpa2b1, Hnrnpu, Hnrnpul1, Prpf8) showed multiple differentially used exons. Thus, Foxa1 and Foxa2 are required during positive selection to regulate alternative splicing of genes essential for T-cell development, and, by also regulating splicing of splicing factors, they exert widespread control of alternative splicing.
AU  - Lau,C-I
AU  - Rowell,J
AU  - Yanez,DC
AU  - Solanki,A
AU  - Ross,S
AU  - Ono,M
AU  - Crompton,T
DO  - 10.1242/dev.199754
PY  - 2021///
TI  - The pioneer transcription factors Foxa1 and Foxa2 regulate alternative RNA splicing during thymocyte positive selection.
T2  - Development
UR  - http://dx.doi.org/10.1242/dev.199754
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34323272
VL  - 148
ER  -
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