Corepressor Rcor1 is essential for murine erythropoiesis

Huilan Yao, Devorah C. Goldman, Tamilla Nechiporuk, Sunita Kawane, Shannon K. McWeeney, Jeffrey W. Tyner, Guang Fan, Marc A. Kerenyi, Stuart H. Orkin, William H. Fleming, Gail Mandel

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 anemicand 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.

Original languageEnglish (US)
Pages (from-to)3175-3184
Number of pages10
JournalBlood
Volume123
Issue number20
DOIs
StatePublished - May 15 2014

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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