Back to Search
Start Over
The Epigenetic Regulator CXXC Finger Protein 1 is Essential for Murine Hematopoiesis
- Source :
- PLoS ONE, PLoS ONE, Vol 9, Iss 12, p e113745 (2014)
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- CXXC finger protein 1 (Cfp1), encoded by the Cxxc1 gene, binds to DNA sequences containing an unmethylated CpG dinucleotide and is an epigenetic regulator of both cytosine and histone methylation. Cxxc1-null mouse embryos fail to gastrulate, and Cxxc1-null embryonic stem cells are viable but cannot differentiate, suggesting that Cfp1 is required for chromatin remodeling associated with stem cell differentiation and embryogenesis. Mice homozygous for a conditional Cxxc1 deletion allele and carrying the inducible Mx1-Cre transgene were generated to assess Cfp1 function in adult animals. Induction of Cre expression in adult animals led to Cfp1 depletion in hematopoietic cells, a failure of hematopoiesis with a nearly complete loss of lineage-committed progenitors and mature cells, elevated levels of apoptosis, and death within two weeks. A similar pathology resulted following transplantation of conditional Cxxc1 bone marrow cells into wild type recipients, demonstrating this phenotype is intrinsic to Cfp1 function within bone marrow cells. Remarkably, the Lin- Sca-1+ c-Kit+ population of cells in the bone marrow, which is enriched for hematopoietic stem cells and multi-potential progenitor cells, persists and expands in the absence of Cfp1 during this time frame. Thus, Cfp1 is necessary for hematopoietic stem and multi-potential progenitor cell function and for the developmental potential of differentiating hematopoietic cells.
- Subjects :
- Male
Myxovirus Resistance Proteins
Cellular differentiation
lcsh:Medicine
Apoptosis
Stem cell factor
Biochemistry
Epigenesis, Genetic
Molecular Cell Biology
Antigens, Ly
lcsh:Science
Cells, Cultured
Bone Marrow Transplantation
Mice, Knockout
Multidisciplinary
Chromosome Biology
Histone Modification
Cell Differentiation
Chromatin
Endothelial stem cell
Proto-Oncogene Proteins c-kit
medicine.anatomical_structure
Epigenetics
Female
Stem cell
DNA modification
Research Article
Adult stem cell
Immunoblotting
Bone Marrow Cells
Mice, Transgenic
Biology
Molecular Genetics
Genetics
medicine
Gene Disruption
Animals
Cell Lineage
Progenitor cell
Molecular Biology
Cell Proliferation
Interleukin 3
Biology and life sciences
lcsh:R
Membrane Proteins
DNA
Cell Biology
Hematopoietic Stem Cells
Molecular biology
Hematopoiesis
Mice, Inbred C57BL
Trans-Activators
lcsh:Q
Bone marrow
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....18fd1544c8f59fb492d1862d79f3add2