title: Friend of GATA (FOG) interacts with the nucleosome remodeling and deacetylase complex (NuRD) to support primitive erythropoiesis in Xenopus laevis.
abstract: Friend of GATA (FOG) plays many diverse roles in adult and embryonic hematopoiesis, however the mechanisms by which it functions and the roles of potential interaction partners are not completely understood. Previous work has shown that overexpression of FOG in Xenopus laevis causes loss of blood suggesting that in contrast to its role in mammals, FOG might normally function to repress erythropoiesis in this species. Using loss-of-function analysis, we demonstrate that FOG is essential to support primitive red blood cell (RBC) development in Xenopus. Moreover, we show that it is specifically required to prevent excess apoptosis of circulating primitive RBCs and that in the absence of FOG, the pro-apoptotic gene Bim-1 is strongly upregulated. To identify domains of FOG that are essential for blood development and, conversely, to begin to understand the mechanism by which overexpressed FOG represses primitive erythropoiesis, we asked whether FOG mutants that are unable to interact with known co-factors retain their ability to rescue blood formation in FOG morphants and whether they repress erythropoiesis when overexpressed in wild type embryos. We find that interaction of FOG with the Nucleosome Remodeling and Deacetylase complex (NuRD), but not with C-terminal Binding Protein, is essential for normal primitive RBC development. In contrast, overexpression of all mutant and wild type constructs causes a comparable repression of primitive erythropoiesis. Together, our data suggest that a requirement for FOG and its interaction with NuRD during primitive erythropoiesis are conserved in Xenopus and that loss of blood upon FOG overexpression is due to a dominant-interfering effect.
authors.affiliation: Department of Cell and Developmental Biology, School of Medicine, Oregon Health and Science University, Portland, Oregon, United States of America.
authors.forename: Mizuho S
authors.initials: MS
authors.lastname: Mimoto
authors.forename: Jan L
authors.initials: JL
authors.lastname: Christian
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival; D004268:DNA-Binding Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis; D005260:Female; D050980:GATA Transcription Factors / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D011485:Protein Binding; D013963:Thyroid Hormones / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D015854:Up-Regulation; D029867:Xenopus Proteins / Q000172:deficiency / Q000378:metabolism*; D014982:Xenopus laevis / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050980:GATA Transcription Factors; D008565:Membrane Proteins; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D009687:Nuclear Proteins; D013963:Thyroid Hormones; D014157:Transcription Factors; D029867:Xenopus Proteins; D000097810:Thyroid Hormone-Binding Proteins; C498429:ZFPM1 protein, Xenopus