First Author | Ghanem LR | Year | 2018 |
Journal | Mol Cell Biol | Volume | 38 |
Issue | 16 | PubMed ID | 29866654 |
Mgi Jnum | J:265272 | Mgi Id | MGI:6199285 |
Doi | 10.1128/MCB.00175-18 | Citation | Ghanem LR, et al. (2018) Poly(C)-Binding Protein Pcbp2 Enables Differentiation of Definitive Erythropoiesis by Directing Functional Splicing of the Runx1 Transcript. Mol Cell Biol 38(16) |
abstractText | Formation of the mammalian hematopoietic system is under a complex set of developmental controls. Here, we report that mouse embryos lacking the KH domain poly(C) binding protein, Pcbp2, are selectively deficient in the definitive erythroid lineage. Compared to wild-type controls, transcript splicing analysis of the Pcbp2(-/-) embryonic liver reveals accentuated exclusion of an exon (exon 6) that encodes a highly conserved transcriptional control segment of the hematopoietic master regulator, Runx1. Embryos rendered homozygous for a Runx1 locus lacking this cassette exon (Runx1DeltaE6) effectively phenocopy the loss of the definitive erythroid lineage in Pcbp2(-/-) embryos. These data support a model in which enhancement of Runx1 cassette exon 6 inclusion by Pcbp2 serves a critical role in development of hematopoietic progenitors and constitutes a critical step in the developmental pathway of the definitive erythropoietic lineage. |