Chun, Kristin T.Li, BinghuiDobrota, ErikaTate, CourtneyLee, Jeong-HeonKhan, ShehnazHaneline, LauraHogenEsch, HarmSkalnik, David G.2016-06-152016-06-152014-12-03Chun, K. T., Li, B., Dobrota, E., Tate, C., Lee, J.-H., Khan, S., … Skalnik, D. G. (2014). The Epigenetic Regulator CXXC Finger Protein 1 is Essential for Murine Hematopoiesis. PLoS ONE, 9(12), e113745. http://doi.org/10.1371/journal.pone.0113745https://hdl.handle.net/1805/9986CXXC 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.en-USPublisher PolicyAntigens, LyApoptosisBone Marrow CellsBone Marrow TransplantationCell DifferentiationCell LineageCell ProliferationHematopoietic Stem CellsMyxovirus Resistance ProteinsArticle