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[A KRAB/KAP1-miRNA cascade regulates erythropoiesis through stage-specific control of mitophagy].

ABSTRACT:

SUBMITTER: Barde I

PROVIDER: S-EPMC4894476 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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[A KRAB/KAP1-miRNA cascade regulates erythropoiesis through stage-specific control of mitophagy].

Barde Isabelle I Rauwel Benjamin B Marin-Florez Ray Marcel RM Corsinotti Andrea A Laurenti Elisa E Verp Sonia S Offner Sandra S Marquis Julien J Kapopoulou Adamandia A Vanicek Jiri J Trono Didier D

Medecine sciences : M/S 20140124 1

PMID: 24472449

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A KRAB/KAP1-miRNA cascade regulates erythropoiesis through stage-specific control of mitophagy.

Project description: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.

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KRAB/KAP1-microRNA cascade regulates erythropoiesis through the stage-specific control of mitophagy

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KRAB/KAP1-microRNA cascade regulates erythropoiesis through the stage-specific control of mitophagy

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PEG3 Interacts with KAP1 through KRAB-A.

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