| First Author | Barde I | Year | 2013 |
| Journal | Science | Volume | 340 |
| Issue | 6130 | Pages | 350-3 |
| PubMed ID | 23493425 | Mgi Jnum | J:195118 |
| Mgi Id | MGI:5476556 | Doi | 10.1126/science.1232398 |
| Citation | Barde I, et al. (2013) A KRAB/KAP1-miRNA cascade regulates erythropoiesis through stage-specific control of mitophagy. Science 340(6130):350-3 |
| abstractText | 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. |
