Publication in detail

Blood 2014 Mar 20. [Epub ahead of print]

The co-repressor Rcor1 is essential for murine erythropoiesis.

Yao, H; Goldman, DC; Nechiporuk, T; Kawane, S; McWeeney, SK; Tyner, TW; Fan, G; Kerenyi, MA; Orkin, SH; Fleming, WH; Mandel, G

Vollum Institute, Howard Hughes Medical Institute, Oregon Health & Science University, Portland, OR, United States

Abstract:
The co-repressor 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 cell (HSC) / progenitor cells. The Colony Stimulating Factor 2 Receptor Beta 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/progenitor genes, as well as the genes and signaling pathways that lead to myeloid cell fate.

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