title: Beta-Actin Is Involved in Modulating Erythropoiesis during Development by Fine-Tuning Gata2 Expression Levels.
abstract: The functions of actin family members during development are poorly understood. To investigate the role of beta-actin in mammalian development, a beta-actin knockout mouse model was used. Homozygous beta-actin knockout mice are lethal at embryonic day (E)10.5. At E10.25 beta-actin knockout embryos are growth retarded and display a pale yolk sac and embryo proper that is suggestive of altered erythropoiesis. Here we report that lack of beta-actin resulted in a block of primitive and definitive hematopoietic development. Reduced levels of Gata2, were associated to this phenotype. Consistently, ChIP analysis revealed multiple binding sites for beta-actin in the Gata2 promoter. Gata2 mRNA levels were almost completely rescued by expression of an erythroid lineage restricted ROSA26-promotor based GATA2 transgene. As a result, erythroid differentiation was restored and the knockout embryos showed significant improvement in yolk sac and embryo vascularization. These results provide new molecular insights for a novel function of beta-actin in erythropoiesis by modulating the expression levels of Gata2 in vivo.
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
authors.forename: Davina
authors.initials: D
authors.lastname: Tondeleir
authors.forename: Benjamin
authors.initials: B
authors.lastname: Drogat
authors.forename: Karolina
authors.initials: K
authors.lastname: Slowicka
authors.forename: Karima
authors.initials: K
authors.lastname: Bakkali
authors.forename: Sonia
authors.initials: S
authors.lastname: Bartunkova
authors.forename: Steven
authors.initials: S
authors.lastname: Goossens
authors.forename: Jody J
authors.initials: JJ
authors.lastname: Haigh
authors.forename: Christophe
authors.initials: C
authors.lastname: Ampe
mesh_terms: D000199:Actins / Q000502:physiology*; D000818:Animals; D001775:Blood Circulation; D002478:Cells, Cultured; D047108:Embryonic Development; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000378:metabolism; D004920:Erythropoiesis / Q000502:physiology*; D005260:Female; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: D000199:Actins; D050989:GATA2 Transcription Factor; C494712:Gata2 protein, mouse