Titill: | POGZ Is Required for Silencing Mouse Embryonic β-like Hemoglobin and Human Fetal Hemoglobin Expression |
Höfundur: |
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Útgáfa: | 2018-06-12 |
Tungumál: | Enska |
Umfang: | 3236-3248 |
Háskóli/Stofnun: | Háskólinn í Reykjavík Reykjavik University |
Svið: | Tækni- og verkfræðideild (HR) School of Science and Engineering (RU) |
Birtist í: | Cell Reports;23(11) |
ISSN: | 2211-1247 |
DOI: | 10.1016/j.celrep.2018.05.043 |
Efnisorð: | General Biochemistry, Genetics and Molecular Biology; Hematopoietic development; Erythropoiesis; Red cells; Globin switching; Fetal globin; Gene regulation; Transcription; Sickle cell disease; β-thalassemia; Lífefnafræði; Erfðafræði; Sameindalíffræði; Blóðkorn; Blóðsjúkdómar; Blóðleysi |
URI: | https://hdl.handle.net/20.500.11815/1313 |
Tilvitnun:Gudmundsdottir, 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.2018.05.043
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Útdráttur:Fetal 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.
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Leyfi:This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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