MOZ and BMI1 act synergistically to maintain Hematopoietic Stem Cells
Journal Title
Experimental Hematology
Publication Type
Journal Article
Abstract
Chromatin plays a central role in maintaining hematopoietic stem cells and during their stepwise differentiation. While a large number of histone modifications and chromatin modifying enzymes have been identified, how these act in concert to produce specific phenotypic outcomes remains to be established. MOZ (KAT6A) is a lysine acetyltransferase and enhances transcription at target gene loci. In contrast, the polycomb group protein BMI1 (PCGF4) is part of the transcriptionally repressive PRC1 complex. Despite their opposing effects on transcription, MOZ and BMI1 regulate biological systems in a similar manner. MOZ and BMI1 are required for the development of transplantable HSCs, for restraining cellular senescence, for the proper patterning of the anterior-posterior axis during development, and for the specification and maintenance of the B cell lineage. Thus, we set out to explore the relationship between MOZ and BMI1. We recently established that MOZ and BMI1 have opposing effects on the initiation of Hox gene expression during embryonic development and that defects in body segment identity specification observed in single Moz and Bmi1 mutants were rescued in compound mutants. We report here the relationship between MOZ and BMI1 in hematopoiesis. Using Moz+/-;Bmi1+/- compound mutant mice, we find that MOZ and BMI1, but not the BMI1-related protein MEL18 (PCGF2), play synergistic roles in maintaining adult HSCs. While BMI1 restrains premature senescence, we establish that MOZ acts to maintain the quiescent state of HSCs. Our work reveals that MOZ and BMI1 regulate HSCs in a synergistic manner by acting on distinct processes required to maintain HSCs.
Publisher
Elsevier
WEHI Research Division(s)
Development And Cancer; Cancer And Haematology
PubMed ID
27773671
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2016-10-26 01:19:30
Last Modified: 2018-07-04 03:22:56
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