E2F-2 Promotes Nuclear Condensation and Enucleation of Terminally Differentiated Erythroblasts. Mol Cell Biol 2017 Jan 01;37(1)
Date
11/01/2016Pubmed ID
27795297Pubmed Central ID
PMC5192079DOI
10.1128/MCB.00274-16Scopus ID
2-s2.0-85008145373 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
E2F-2 is a retinoblastoma (Rb)-regulated transcription factor induced during terminal erythroid maturation. Cyclin E-mediated Rb hyperphosphorylation induces E2F transcriptional activator functions. We previously reported that deregulated cyclin E activity causes defective terminal maturation of nucleated erythroblasts in vivo Here, we found that these defects are normalized by E2F-2 deletion; however, anemia in mice with deregulated cyclin E is not improved by E2F-2-loss, which itself causes reduced peripheral red blood cell (RBC) counts without altering relative abundances of erythroblast subpopulations. To determine how E2F-2 regulates RBC production, we comprehensively studied erythropoiesis using knockout mice and hematopoietic progenitors. We found that efficient stress erythropoiesis in vivo requires E2F-2, and we also identified an unappreciated role for E2F-2 in erythroblast enucleation. In particular, E2F-2 deletion impairs nuclear condensation, a morphological feature of maturing erythroblasts. Transcriptome profiling of E2F-2-null, mature erythroblasts demonstrated widespread changes in gene expression. Notably, we identified citron Rho-interacting kinase (CRIK), which has known functions in mitosis and cytokinesis, as induced in erythroblasts in an E2F-2-dependent manner, and we found that CRIK activity promotes efficient erythroblast enucleation and nuclear condensation. Together, our data reveal novel, lineage-specific functions for E2F-2 and suggest that some mitotic kinases have specialized roles supporting enucleation of maturing erythroblasts.
Author List
Swartz KL, Wood SN, Murthy T, Ramirez O, Qin G, Pillai MM, Rao S, Minella ACAuthor
Sridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Cycle
Cell Differentiation
Cell Nucleus
Cyclin E
E2F2 Transcription Factor
Erythroblasts
Erythropoiesis
Gene Deletion
Gene Expression Profiling
Gene Expression Regulation
Intracellular Signaling Peptides and Proteins
Mice
Phosphorylation
Retinoblastoma Protein
