Publication Date:
2013-03-16
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678075/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678075/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barde, Isabelle -- Rauwel, Benjamin -- Marin-Florez, Ray Marcel -- Corsinotti, Andrea -- Laurenti, Elisa -- Verp, Sonia -- Offner, Sandra -- Marquis, Julien -- Kapopoulou, Adamandia -- Vanicek, Jiri -- Trono, Didier -- 268721/European Research Council/International -- New York, N.Y. -- Science. 2013 Apr 19;340(6130):350-3. doi: 10.1126/science.1232398. Epub 2013 Mar 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23493425" target="_blank"〉PubMed〈/a〉
Keywords:
Anemia/genetics
;
Animals
;
Autophagy/*genetics
;
Erythroblasts/*metabolism/ultrastructure
;
Erythropoiesis/*genetics
;
Female
;
Male
;
Membrane Proteins/metabolism
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
MicroRNAs/genetics/*metabolism
;
Mitochondria/genetics/*physiology
;
Mitochondrial Proteins/metabolism
;
Nuclear Proteins/genetics/*metabolism
;
Repressor Proteins/genetics/*metabolism
;
Transcription Factors/*metabolism
;
*Zinc Fingers
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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