title: The epigenetic regulator CXXC finger protein 1 is essential for murine hematopoiesis.
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.
authors.affiliation: Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Biology Department, Indiana University-Purdue University Indianapolis School of Science, Indianapolis, Indiana, United States of America.
authors.forename: Kristin T
authors.initials: KT
authors.lastname: Chun
authors.affiliation: Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Binghui
authors.initials: B
authors.lastname: Li
authors.affiliation: Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Erika
authors.initials: E
authors.lastname: Dobrota
authors.affiliation: Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Courtney
authors.initials: C
authors.lastname: Tate
authors.affiliation: Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Jeong-Heon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Shehnaz
authors.initials: S
authors.lastname: Khan
authors.affiliation: Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Departments of Microbiology & Immunology and Cellular & Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Haneline
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Harm
authors.initials: H
authors.lastname: HogenEsch
authors.affiliation: Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Biology Department, Indiana University-Purdue University Indianapolis School of Science, Indianapolis, Indiana, United States of America.
authors.forename: David G
authors.initials: DG
authors.lastname: Skalnik
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D044127:Epigenesis, Genetic; D005260:Female; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D015151:Immunoblotting; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; C501971:Cxxc1 protein, mouse; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D015534:Trans-Activators; D019009:Proto-Oncogene Proteins c-kit