Details

Autor(en) / Beteiligte

• Ghanem, Louis R.
• Kromer, Andrew
• Silverman, Ian M.
• Ji, Xinjun
• Gazzara, Matthew
• Nguyen, Nhu
• Aguilar, Gabrielle
• Martinelli, Massimo
• Barash, Yoseph
• Liebhaber, Stephen A.

Titel

Poly(C)-Binding Protein Pcbp2 Enables Differentiation of Definitive Erythropoiesis by Directing Functional Splicing of the Runx1 Transcript

Ist Teil von

• Molecular and cellular biology, 2018-08, Vol.38 (16)

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2018

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 (Runx1ΔE6) 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.