Selective deployment of transcription factor paralogs with submaximal strength facilitates gene regulation in the immune system
Details
Publication Year 2019-08-26, Volume 20, Issue #10, Page 1372-1380
Journal Title
Nature Immunology
Publication Type
Journal Article
Abstract
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 nonequivalence 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 toward submaximal 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.
Publisher
Springer Nature
WEHI Research Division(s)
Immunology
PubMed ID
31451789
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2019-09-20 10:16:28
Last Modified: 2019-09-24 03:13:23
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