A KRAB/KAP1-miRNA Cascade Regulates Erythropoiesis Through Stage-Specific Control of Mitophagy

Détails

Ressource 1Télécharger: BIB_46F2FB0DD990.P001.pdf (1707.09 [Ko])
Etat: Serval
Version: Author's accepted manuscript
ID Serval
serval:BIB_46F2FB0DD990
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A KRAB/KAP1-miRNA Cascade Regulates Erythropoiesis Through Stage-Specific Control of Mitophagy
Périodique
Science (new York, N.y.)
Auteur(s)
Barde I., Rauwel B., Marin-Florez R.M., Corsinotti A., Laurenti E., Verp S., Offner S., Marquis J., Kapopoulou A., Vanicek J., Trono D.
ISSN
0036-8075 (Print)
1095-9203 (Electronic)
ISSN-L
0036-8075
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
340
Numéro
6130
Pages
350-353
Langue
anglais
Notes
Publication types: Article ; research-article Identifiant PubMed Central: PMC3678075
Résumé
During hematopoiesis, lineage- and stage-specific transcription factors work in concert with chromatin modifiers to direct the differentiation of all blood cells. We explored the role of KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor KAP1 in this process. In mice, hematopoietic-restricted deletion of Kap1 resulted in severe hypoproliferative anemia. Kap1-deleted erythroblasts failed to induce mitophagy-associated genes and retained mitochondria. This was due to persistent expression of microRNAs (miRNAs) targeting mitophagy transcripts, itself secondary to a lack of repression by stage-specific KRAB-ZFPs. The KRAB/KAP1-miRNA regulatory cascade is evolutionarily conserved, as it also controls mitophagy during human erythropoiesis. Thus, a multilayered transcription regulatory system is present, in which protein- and RNA-based repressors are superimposed in combinatorial fashion to govern the timely triggering of an important differentiation event.
Mots-clé
Anemia/genetics, Autophagy/genetics, Erythroblasts/metabolism, Erythroblasts/ultrastructure, Erythropoiesis/genetics, Membrane Proteins/metabolism, MicroRNAs/genetics, MicroRNAs/metabolism, Mitochondria/genetics, Mitochondria/physiology, Mitochondrial Proteins/metabolism, Nuclear Proteins/genetics, Nuclear Proteins/metabolism, Repressor Proteins/genetics, Repressor Proteins/metabolism, Transcription Factors/metabolism
Pubmed
Web of science
Création de la notice
11/07/2016 11:04
Dernière modification de la notice
03/03/2018 16:48
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