A KRAB/KAP1-miRNA cascade regulates erythropoiesis through stage-specific control of mitophagy.
Science
; 340(6130): 350-3, 2013 Apr 19.
Article
em En
| MEDLINE
| ID: mdl-23493425
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Autofagia
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Fatores de Transcrição
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Proteínas Nucleares
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Eritroblastos
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Dedos de Zinco
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MicroRNAs
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Eritropoese
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Mitocôndrias
Limite:
Animals
Idioma:
En
Revista:
Science
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
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