Imperial College London

Professor Dame Amanda Fisher

Faculty of MedicineInstitute of Clinical Sciences

Head of the Institute of Clinical Sciences
 
 
 
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Contact

 

amanda.fisher

 
 
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Assistant

 

Ms Alessandra Lisini +44 (0)20 3313 8236

 
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Location

 

CRB (Clinical Research Building)Hammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bruno,
author = {Bruno, L and Ramlall, V and Studer, RA and Sauer, S and Bradley, D and Dharmalingam, G and Carroll, T and Ghoneim, M and Chopin, M and Nutt, SL and Elderkin, S and Rueda, DS and Fisher, AG and Siggers, T and Beltrao, P and Merkenschlager, M},
journal = {Nature Immunology},
title = {Selective deployment of transcription factor paralogs with submaximal strength facilitates gene regulation in the immune system},
url = {http://hdl.handle.net/10044/1/71508},
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - In multicellular organisms, duplicated genes can diverge through tissue-specific gene expression patterns, as exemplified by highly regulated expression of Runx transcription factor paralogs with apparent functional redundancy. Here we asked what cell type-specific biologies might be supported by the selective expression of Runx paralogs during Langerhans cell and inducible regulatory T cell differentiation. We uncovered functional non-equivalence between Runx paralogs. Selective expression of native paralogs allowed integration of transcription factor activity with extrinsic signals, while non-native paralogs enforced differentiation even in the absence of exogenous inducers. DNA-binding affinity was controlled by divergent amino acids within the otherwise highly conserved RUNT domain, and evolutionary reconstruction suggested convergence of RUNT domain residues towards sub-maximal strength. Hence, the selective expression of gene duplicates in specialized cell types can synergize with the acquisition of functional differences to enable appropriate gene expression, lineage choice and differentiation in the mammalian immune system.
AU - Bruno,L
AU - Ramlall,V
AU - Studer,RA
AU - Sauer,S
AU - Bradley,D
AU - Dharmalingam,G
AU - Carroll,T
AU - Ghoneim,M
AU - Chopin,M
AU - Nutt,SL
AU - Elderkin,S
AU - Rueda,DS
AU - Fisher,AG
AU - Siggers,T
AU - Beltrao,P
AU - Merkenschlager,M
SN - 1529-2908
TI - Selective deployment of transcription factor paralogs with submaximal strength facilitates gene regulation in the immune system
T2 - Nature Immunology
UR - http://hdl.handle.net/10044/1/71508
ER -