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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.

Titel:	Corepressor Rcor1 is essential for murine erythropoiesis.
Autor/in / Beteiligte Person:	Yao, H ; Goldman, DC ; Nechiporuk, T ; Kawane, S ; McWeeney, SK ; Tyner, JW ; Fan, G ; Kerenyi, MA ; Orkin, SH ; Fleming, WH ; Mandel, G
Zeitschrift:	Blood, Jg. 123 (2014-05-15), Heft 20, S. 3175-84
Veröffentlichung:	2021- : [New York] : Elsevier ; <i>Original Publication</i>: New York, Grune & Stratton [etc.], 2014
Medientyp:	academicJournal
ISSN:	1528-0020 (electronic)
DOI:	10.1182/blood-2013-11-538678
Schlagwort:	Animals Cells, Cultured Co-Repressor Proteins genetics Cytokine Receptor Common beta Subunit metabolism Embryo, Mammalian metabolism Embryo, Mammalian pathology Erythroblasts cytology Erythroblasts metabolism Erythroid Precursor Cells cytology Erythroid Precursor Cells metabolism Erythroid Precursor Cells pathology Gene Deletion Gene Expression Regulation, Developmental Mice Mice, Knockout Myeloid Cells cytology Receptors, Interleukin-3 metabolism Signal Transduction Co-Repressor Proteins metabolism Erythropoiesis
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Blood] 2014 May 15; Vol. 123 (20), pp. 3175-84. <i>Date of Electronic Publication: </i>2014 Mar 20. MeSH Terms: Erythropoiesis* ; Co-Repressor Proteins / *metabolism ; Animals ; Cells, Cultured ; Co-Repressor Proteins / genetics ; Cytokine Receptor Common beta Subunit / metabolism ; Embryo, Mammalian / metabolism ; Embryo, Mammalian / pathology ; Erythroblasts / cytology ; Erythroblasts / metabolism ; Erythroid Precursor Cells / cytology ; Erythroid Precursor Cells / metabolism ; Erythroid Precursor Cells / pathology ; Gene Deletion ; Gene Expression Regulation, Developmental ; Mice ; Mice, Knockout ; Myeloid Cells / cytology ; Receptors, Interleukin-3 / metabolism ; Signal Transduction References: Neuron. 2001 Aug 16;31(3):353-65. (PMID: 11516394) ; Nature. 2007 Apr 19;446(7138):882-7. (PMID: 17392792) ; Mol Cell. 2007 Aug 17;27(4):562-72. (PMID: 17707228) ; J Biol Chem. 1995 Jul 28;270(30):17939-46. (PMID: 7629100) ; Blood. 2010 Apr 8;115(14):2784-95. (PMID: 20124515) ; Nature. 2005 Sep 15;437(7057):432-5. (PMID: 16079794) ; J Immunol. 2005 Jun 1;174(11):7014-21. (PMID: 15905544) ; Genes Dev. 1999 Jun 1;13(11):1398-411. (PMID: 10364157) ; Blood. 1996 Jan 15;87(2):479-90. (PMID: 8555469) ; Blood. 1997 Aug 15;90(4):1471-81. (PMID: 9269764) ; Blood. 2012 Jul 12;120(2):335-46. (PMID: 22665933) ; Genes Dev. 1993 Jun;7(6):1097-109. (PMID: 8504932) ; Leukemia. 2000 Mar;14(3):439-45. (PMID: 10720139) ; Blood Cells Mol Dis. 2003 Mar-Apr;30(2):164-9. (PMID: 12732179) ; Science. 2011 Nov 18;334(6058):993-6. (PMID: 21998251) ; Genes Dev. 2002 Feb 1;16(3):301-6. (PMID: 11825872) ; Mol Cell Biol. 2005 Aug;25(15):6355-62. (PMID: 16024775) ; Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10141-6. (PMID: 19497860) ; Genome Res. 2010 Aug;20(8):1064-83. (PMID: 20566737) ; Br J Haematol. 2006 Oct;135(2):242-53. (PMID: 16939493) ; Int J Biochem Cell Biol. 1999 Oct;31(10):1011-5. (PMID: 10582335) ; Cancer Cell. 2008 Apr;13(4):311-20. (PMID: 18394554) ; Cell Stem Cell. 2008 May 8;2(5):484-96. (PMID: 18462698) ; Blood. 2003 Dec 1;102(12):3938-46. (PMID: 12907435) ; Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9873-8. (PMID: 10449787) ; Blood. 1999 Jan 15;93(2):488-99. (PMID: 9885210) ; Cancer Res. 2007 Jan 15;67(2):537-45. (PMID: 17234761) ; Genesis. 2000 Feb;26(2):113-5. (PMID: 10686601) ; Blood. 2011 Dec 8;118(24):6258-68. (PMID: 21998215) ; Science. 1995 Sep 8;269(5229):1427-9. (PMID: 7660125) ; Cell Stem Cell. 2007 Oct 11;1(4):428-42. (PMID: 18371379) ; IUBMB Life. 2009 Aug;61(8):800-30. (PMID: 19621348) ; J Clin Invest. 1998 Dec 1;102(11):1951-60. (PMID: 9835620) ; Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517) ; Cell Stem Cell. 2007 Nov;1(5):578-91. (PMID: 18371395) ; Blood. 2001 Aug 1;98(3):627-35. (PMID: 11468160) ; Haematologica. 2011 Sep;96(9):1252-60. (PMID: 21606163) ; EMBO J. 2002 Jun 3;21(11):2672-81. (PMID: 12032080) ; Nature. 2006 Aug 17;442(7104):818-22. (PMID: 16862118) ; Oncogene. 2007 Oct 15;26(47):6816-28. (PMID: 17934488) ; Nature. 1994 Sep 15;371(6494):221-6. (PMID: 8078582) ; Mutat Res. 2008 Dec 1;647(1-2):68-76. (PMID: 18760288) ; Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6518-23. (PMID: 23576758) ; PLoS One. 2013;8(1):e53666. (PMID: 23308270) ; Proc Natl Acad Sci U S A. 2002 May 28;99(11):7420-5. (PMID: 12032298) ; Blood. 1998 Nov 15;92(10):3636-46. (PMID: 9808557) ; Nat Biotechnol. 2010 Oct;28(10):1069-78. (PMID: 20944599) ; J Immunol. 1999 Sep 1;163(5):2674-80. (PMID: 10453008) ; J Biol Chem. 2001 Mar 2;276(9):6817-24. (PMID: 11102443) ; Blood. 2004 Apr 1;103(7):2522-9. (PMID: 14630789) ; Mol Cell. 2006 Aug 4;23(3):377-87. (PMID: 16885027) ; Blood. 2001 Dec 15;98(13):3618-25. (PMID: 11739165) ; Elife. 2013 Jun 18;2:e00633. (PMID: 23795291) ; Dev Biol. 2005 Apr 15;280(2):307-20. (PMID: 15882575) Grant Information: R01 HL032259 United States HL NHLBI NIH HHS; United States HHMI Howard Hughes Medical Institute; 5P30CA069533 United States CA NCI NIH HHS; R01 HL069133 United States HL NHLBI NIH HHS; UL1 RR024140 United States RR NCRR NIH HHS; R01 NS022518 United States NS NINDS NIH HHS; HL069133 United States HL NHLBI NIH HHS; NS22518 United States NS NINDS NIH HHS; P30 CA069533 United States CA NCI NIH HHS; 5UL1RR024140 United States RR NCRR NIH HHS Substance Nomenclature: 0 (Co-Repressor Proteins) ; 0 (Cytokine Receptor Common beta Subunit) ; 0 (Rcor1 protein, mouse) ; 0 (Receptors, Interleukin-3) ; 144715-96-8 (Csf2rb2 protein, mouse) ; 144715-98-0 (Csf2rb protein, mouse) Entry Date(s): Date Created: 20140322 Date Completed: 20140715 Latest Revision: 20211021 Update Code: 20231215 PubMed Central ID: PMC4023423

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Corepressor Rcor1 is essential for murine erythropoiesis.