Háskólinn í ReykjavíkReykjavik UniversityGudmundsdottir, BjorgGudmundsson, Kristbjorn OrriKlarmann, Kimberly D.Singh, Satyendra K.Sun, LeiSingh, ShwetaDu, YangCoppola, VincenzoStockwin, LukeNguyen, NhuTessarollo, LinoThorsteinsson, LeifurSigurjonsson, OlafurGudmundsson, Sveinn VidarRafnar, ThorunnTisdale, John F.Keller, Jonathan R.2019-10-242019-10-242018-06-12Gudmundsdottir, B., Gudmundsson, K. O., Klarmann, K. D., Singh, S. K., Sun, L., Singh, S., … Keller, J. R. (2018). POGZ Is Required for Silencing Mouse Embryonic β-like Hemoglobin and Human Fetal Hemoglobin Expression. Cell Reports, 23(11), 3236–3248. https://doi.org/10.1016/j.celrep.2018.05.0432211-1247https://hdl.handle.net/20.500.11815/1313Fetal globin genes are transcriptionally silenced during embryogenesis through hemoglobin switching. Strategies to derepress fetal globin expression in the adult could alleviate symptoms in sickle cell disease and β-thalassemia. We identified a zinc-finger protein, pogo transposable element with zinc-finger domain (POGZ), expressed in hematopoietic progenitor cells. Targeted deletion of Pogz in adult hematopoietic cells in vivo results in persistence of embryonic β-like globin expression without affecting erythroid development. POGZ binds to the Bcl11a promoter and erythroid-specific intragenic regulatory regions. Pogz+/− mice show elevated embryonic β-like globin expression, suggesting that partial reduction of Pogz expression results in persistence of embryonic β-like globin expression. Knockdown of POGZ in primary human CD34+ progenitor cell-derived erythroblasts reduces BCL11A expression, a known repressor of embryonic β-like globin expression, and increases fetal hemoglobin expression. These findings are significant, since new therapeutic targets and strategies are needed to treat β-globin disorders.3236-3248eninfo:eu-repo/semantics/openAccessGeneral Biochemistry, Genetics and Molecular BiologyHematopoietic developmentErythropoiesisRed cellsGlobin switchingFetal globinGene regulationTranscriptionSickle cell diseaseβ-thalassemiaLífefnafræðiErfðafræðiSameindalíffræðiBlóðkornBlóðsjúkdómarBlóðleysiinfo:eu-repo/semantics/article10.1016/j.celrep.2018.05.043