title: The exosome complex establishes a barricade to erythroid maturation.
abstract: Complex genetic networks control hematopoietic stem cell differentiation into progenitors that give rise to billions of erythrocytes daily. Previously, we described a role for the master regulator of erythropoiesis, GATA-1, in inducing genes encoding components of the autophagy machinery. In this context, the Forkhead transcription factor, Foxo3, amplified GATA-1-mediated transcriptional activation. To determine the scope of the GATA-1/Foxo3 cooperativity, and to develop functional insights, we analyzed the GATA-1/Foxo3-dependent transcriptome in erythroid cells. GATA-1/Foxo3 repressed expression of Exosc8, a pivotal component of the exosome complex, which mediates RNA surveillance and epigenetic regulation. Strikingly, downregulating Exosc8, or additional exosome complex components, in primary erythroid precursor cells induced erythroid cell maturation. Our results demonstrate a new mode of controlling erythropoiesis in which multiple components of the exosome complex are endogenous suppressors of the erythroid developmental program.
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison Blood Research Program, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;
authors.forename: Skye C
authors.initials: SC
authors.lastname: McIver
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison Blood Research Program, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;
authors.forename: Yoon-A
authors.initials: YA
authors.lastname: Kang
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison Blood Research Program, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;
authors.forename: Andrew W
authors.initials: AW
authors.lastname: DeVilbiss
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison Blood Research Program, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;
authors.forename: Chelsea A
authors.initials: CA
authors.lastname: O'Driscoll
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison Blood Research Program, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Ouellette
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison Blood Research Program, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;
authors.forename: Nathaniel J
authors.initials: NJ
authors.lastname: Pope
authors.affiliation: Department of Developmental and Regenerative Biology, Mt. Sinai School of Medicine, New York, NY;
authors.forename: Genis
authors.initials: G
authors.lastname: Camprecios
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, New York, NY; and.
authors.forename: Chan-Jung
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: Department of Pathology, University of Wisconsin School of Medicine and Public Health, Madison WI.
authors.forename: David
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, New York, NY; and.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Bouhassira
authors.affiliation: Department of Developmental and Regenerative Biology, Mt. Sinai School of Medicine, New York, NY;
authors.forename: Saghi
authors.initials: S
authors.lastname: Ghaffari
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison Blood Research Program, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;
authors.forename: Emery H
authors.initials: EH
authors.lastname: Bresnick
mesh_terms: D000818:Animals; D001343:Autophagy; D002454:Cell Differentiation; D044127:Epigenesis, Genetic; D004900:Erythroblasts / Q000166:cytology; D004912:Erythrocytes / Q000166:cytology*; D041905:Erythroid Cells / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics; D055354:Exosomes / Q000502:physiology*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D012313:RNA / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D012313:RNA