The KDM4/JMJD2 histone demethylases are required for hematopoietic stem cell maintenance Journal Article


Authors: Agger, K.; Nishimura, K.; Miyagi, S.; Messling, J. E.; Rasmussen, K. D.; Helin, K.
Article Title: The KDM4/JMJD2 histone demethylases are required for hematopoietic stem cell maintenance
Abstract: KDM4/JMJD2 are H3K9- and H3K36-specific demethylases, which are considered promising therapeutic targets for the treatment of acute myeloid leukemia (AML) harboring MLL translocations. Here, we investigate the long-term effects of depleting KDM4 activity on normal hematopoiesis to probe potential side effects of continuous inhibition of these enzymes. Utilizing conditional Kdm4a/Kdm4b/Kdm4c triple-knockout mice, we show that KDM4 activity is required for hematopoietic stem cell (HSC) maintenance in vivo. The knockout of the KDM4 demethylases leads to accumulation of H3K9me3 on transcription start sites and the corresponding downregulation of expression of several genes in HSCs. We show that 2 of these genes, Taf1b and Nom1, are essential for the maintenance of hematopoietic cells. Taken together, our results show that the KDM4 demethylases are required for the expression of genes essential for the long-term maintenance of normal hematopoiesis. © 2019 American Society of Hematology. All rights reserved.
Journal Title: Blood
Volume: 134
Issue: 14
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2019-10-03
Start Page: 1154
End Page: 1158
Language: English
DOI: 10.1182/blood.2019000855
PUBMED: 31434704
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 November 2019 -- Source: Scopus
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  1. Kristian Helin
    4 Helin