title: Corepressor Rcor1 is essential for murine erythropoiesis.
abstract: The corepressor Rcor1 has been linked biochemically to hematopoiesis, but its function in vivo remains unknown. We show that mice deleted for Rcor1 are profoundly anemic and die in late gestation. Definitive erythroid cells from mutant mice arrest at the transition from proerythroblast to basophilic erythroblast. Remarkably, Rcor1 null erythroid progenitors cultured in vitro form myeloid colonies instead of erythroid colonies. The mutant proerythroblasts also aberrantly express genes of the myeloid lineage as well as genes typical of hematopoietic stem cells (HSCs) and/or progenitor cells. The colony-stimulating factor 2 receptor β subunit (Csf2rb), which codes for a receptor implicated in myeloid cytokine signaling, is a direct target for both Rcor1 and the transcription repressor Gfi1b in erythroid cells. In the absence of Rcor1, the Csf2rb gene is highly induced, and Rcor1(-/-) progenitors exhibit CSF2-dependent phospho-Stat5 hypersensitivity. Blocking this pathway can partially reduce myeloid colony formation by Rcor1-deficient erythroid progenitors. Thus, Rcor1 promotes erythropoiesis by repressing HSC and/or progenitor genes, as well as the genes and signaling pathways that lead to myeloid cell fate.
authors.affiliation: Vollum Institute.
authors.forename: Huilan
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Pediatrics, Oregon Stem Cell Center, Knight Cancer Institute.
authors.forename: Devorah C
authors.initials: DC
authors.lastname: Goldman
authors.affiliation: Vollum Institute.
authors.forename: Tamilla
authors.initials: T
authors.lastname: Nechiporuk
authors.affiliation: Oregon Clinical and Translational Research Institute.
authors.forename: Sunita
authors.initials: S
authors.lastname: Kawane
authors.affiliation: Knight Cancer Institute, Oregon Clinical and Translational Research Institute, Division of Bioinformatics and Computational Biology.
authors.forename: Shannon K
authors.initials: SK
authors.lastname: McWeeney
authors.affiliation: Knight Cancer Institute, Department of Cell and Developmental Biology.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Tyner
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, OR;
authors.forename: Guang
authors.initials: G
authors.lastname: Fan
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA;
authors.forename: Marc A
authors.initials: MA
authors.lastname: Kerenyi
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA; Howard Hughes Medical Institute, Boston, MA; and.
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
authors.affiliation: Department of Pediatrics, Oregon Stem Cell Center, Knight Cancer Institute.
authors.forename: William H
authors.initials: WH
authors.lastname: Fleming
authors.affiliation: Vollum Institute, Howard Hughes Medical Institute, Portland, OR.
authors.forename: Gail
authors.initials: G
authors.lastname: Mandel
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D053648:Cytokine Receptor Common beta Subunit / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D004920:Erythropoiesis; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D056970:Co-Repressor Proteins; D053648:Cytokine Receptor Common beta Subunit; C000589468:Rcor1 protein, mouse; D016185:Receptors, Interleukin-3; C072185:Csf2rb2 protein, mouse; C072186:Csf2rb protein, mouse