Selective deployment of transcription factor paralogs with submaximal strength facilitates gene regulation in the immune system.
Animals
Cell Differentiation
Cell Lineage
Conserved Sequence
Core Binding Factor alpha Subunits
/ genetics
Evolution, Molecular
Gene Duplication
Humans
Immune System
/ physiology
Langerhans Cells
/ physiology
Mammals
Organ Specificity
/ genetics
Signal Transduction
T-Lymphocytes, Regulatory
/ physiology
Transcriptome
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
15
05
2018
accepted:
16
07
2019
pubmed:
28
8
2019
medline:
7
3
2020
entrez:
28
8
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31451789
doi: 10.1038/s41590-019-0471-5
pii: 10.1038/s41590-019-0471-5
pmc: PMC6754753
mid: EMS83752
doi:
Substances chimiques
Core Binding Factor alpha Subunits
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1372-1380Subventions
Organisme : Medical Research Council
ID : MC_U120027516
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 099276
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_1102/5
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI116829
Pays : United States
Commentaires et corrections
Type : CommentIn
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