In:
Science, American Association for the Advancement of Science (AAAS), Vol. 340, No. 6130 ( 2013-04-19), p. 350-353
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.1232398
Sprache:
Englisch
Verlag:
American Association for the Advancement of Science (AAAS)
Publikationsdatum:
2013
ZDB Id:
128410-1
ZDB Id:
2066996-3
ZDB Id:
2060783-0
SSG:
11