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The ISWI ATPase Smarca5 (Snf2h) Is Required for Proliferation and Differentiation of Hematopoietic Stem and Progenitor Cells
J. Kokavec, T. Zikmund, F. Savvulidi, V. Kulvait, W. Edelmann, AI. Skoultchi, T. Stopka,
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural
Grant support
NV16-27790A
MZ0
CEP Register
Digital library NLK
Full text - Article
NLK
Free Medical Journals
from 1996 to 1 year ago
Wiley Free Content
from 1996 to 2021
PubMed
28276606
DOI
10.1002/stem.2604
Knihovny.cz E-resources
- MeSH
- Adenosine Triphosphatases deficiency metabolism MeSH
- Anemia pathology MeSH
- Cell Differentiation * MeSH
- Cell Cycle MeSH
- Chromosomal Proteins, Non-Histone deficiency metabolism MeSH
- Gene Deletion MeSH
- Erythroid Cells cytology MeSH
- Erythropoiesis MeSH
- Genotype MeSH
- Hematopoietic Stem Cells cytology metabolism MeSH
- Hematopoiesis MeSH
- RNA, Messenger genetics metabolism MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout MeSH
- Tumor Suppressor Protein p53 metabolism MeSH
- DNA Damage genetics MeSH
- Cell Proliferation MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
The imitation switch nuclear ATPase Smarca5 (Snf2h) is one of the most conserved chromatin remodeling factors. It exists in a variety of oligosubunit complexes that move DNA with respect to the histone octamer to generate regularly spaced nucleosomal arrays. Smarca5 interacts with different accessory proteins and represents a molecular motor for DNA replication, repair, and transcription. We deleted Smarca5 at the onset of definitive hematopoiesis (Vav1-iCre) and observed that animals die during late fetal development due to anemia. Hematopoietic stem and progenitor cells accumulated but their maturation toward erythroid and myeloid lineages was inhibited. Proerythroblasts were dysplastic while basophilic erythroblasts were blocked in G2/M and depleted. Smarca5 deficiency led to increased p53 levels, its activation at two residues, one associated with DNA damage (S15Ph°s) second with CBP/p300 (K376Ac), and finally activation of the p53 targets. We also deleted Smarca5 in committed erythroid cells (Epor-iCre) and observed that animals were anemic postnatally. Furthermore, 4-hydroxytamoxifen-mediated deletion of Smarca5 in the ex vivo cultures confirmed its requirement for erythroid cell proliferation. Thus, Smarca5 plays indispensable roles during early hematopoiesis and erythropoiesis. Stem Cells 2017;35:1614-1623.
BIOCEV 1st Faculty of Medicine Charles University Czech Republic
Department of Cell Biology Albert Einstein College of Medicine Bronx New York USA
References provided by Crossref.org
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