Repressive Gene Regulation Synchronizes Development with Cellular Metabolism.
Animals
Animals, Genetically Modified
Brain
/ cytology
Drosophila melanogaster
/ genetics
Eye
/ cytology
Female
Gene Expression Regulation, Developmental
Gene Regulatory Networks
Insulin
/ metabolism
Loss of Function Mutation
MicroRNAs
/ metabolism
Models, Theoretical
Neurons
/ metabolism
Repressor Proteins
/ genetics
Transcription, Genetic
Drosophila
control theory
development
mathematical modeling
metabolism
microRNA
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
08 08 2019
08 08 2019
Historique:
received:
13
02
2019
revised:
06
05
2019
accepted:
12
06
2019
pubmed:
30
7
2019
medline:
10
5
2020
entrez:
30
7
2019
Statut:
ppublish
Résumé
Metabolic conditions affect the developmental tempo of animals. Developmental gene regulatory networks (GRNs) must therefore synchronize their dynamics with a variable timescale. We find that layered repression of genes couples GRN output with variable metabolism. When repressors of transcription or mRNA and protein stability are lost, fewer errors in Drosophila development occur when metabolism is lowered. We demonstrate the universality of this phenomenon by eliminating the entire microRNA family of repressors and find that development to maturity can be largely rescued when metabolism is reduced. Using a mathematical model that replicates GRN dynamics, we find that lowering metabolism suppresses the emergence of developmental errors by curtailing the influence of auxiliary repressors on GRN output. We experimentally show that gene expression dynamics are less affected by loss of repressors when metabolism is reduced. Thus, layered repression provides robustness through error suppression and may provide an evolutionary route to a shorter reproductive cycle.
Identifiants
pubmed: 31353220
pii: S0092-8674(19)30686-5
doi: 10.1016/j.cell.2019.06.023
pmc: PMC6865806
mid: NIHMS1535146
pii:
doi:
Substances chimiques
Insulin
0
MicroRNAs
0
Repressor Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
980-992.e17Subventions
Organisme : NIGMS NIH HHS
ID : P50 GM081892
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118144
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA080621
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008061
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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