dc.contributor |
Háskólinn í Reykjavík |
dc.contributor |
Reykjavik University |
dc.contributor.author |
Gudmundsdottir, Bjorg |
dc.contributor.author |
Gudmundsson, Kristbjorn Orri |
dc.contributor.author |
Klarmann, Kimberly D. |
dc.contributor.author |
Singh, Satyendra K. |
dc.contributor.author |
Sun, Lei |
dc.contributor.author |
Singh, Shweta |
dc.contributor.author |
Du, Yang |
dc.contributor.author |
Coppola, Vincenzo |
dc.contributor.author |
Stockwin, Luke |
dc.contributor.author |
Nguyen, Nhu |
dc.contributor.author |
Tessarollo, Lino |
dc.contributor.author |
Thorsteinsson, Leifur |
dc.contributor.author |
Sigurjonsson, Olafur |
dc.contributor.author |
Gudmundsson, Sveinn Vidar |
dc.contributor.author |
Rafnar, Thorunn |
dc.contributor.author |
Tisdale, John F. |
dc.contributor.author |
Keller, Jonathan R. |
dc.date.accessioned |
2019-10-24T10:19:57Z |
dc.date.available |
2019-10-24T10:19:57Z |
dc.date.issued |
2018-06-12 |
dc.identifier.citation |
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 |
dc.identifier.issn |
2211-1247 |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/1313 |
dc.description.abstract |
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. |
dc.description.sponsorship |
This project was funded in part by federal funds from the Frederick National Laboratory for Cancer Research, NIH (contract HHSN261200800001E) and by the intramural research program of the NHLBI and NIDDK, NIH (HL006009-09) and USUHS (R086414217). |
dc.format.extent |
3236-3248 |
dc.language.iso |
en |
dc.publisher |
Elsevier BV |
dc.relation.ispartofseries |
Cell Reports;23(11) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
General Biochemistry, Genetics and Molecular Biology |
dc.subject |
Hematopoietic development |
dc.subject |
Erythropoiesis |
dc.subject |
Red cells |
dc.subject |
Globin switching |
dc.subject |
Fetal globin |
dc.subject |
Gene regulation |
dc.subject |
Transcription |
dc.subject |
Sickle cell disease |
dc.subject |
β-thalassemia |
dc.subject |
Lífefnafræði |
dc.subject |
Erfðafræði |
dc.subject |
Sameindalíffræði |
dc.subject |
Blóðkorn |
dc.subject |
Blóðsjúkdómar |
dc.subject |
Blóðleysi |
dc.title |
POGZ Is Required for Silencing Mouse Embryonic β-like Hemoglobin and Human Fetal Hemoglobin Expression |
dc.type |
info:eu-repo/semantics/article |
dcterms.license |
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
dc.description.version |
Peer reviewed |
dc.identifier.doi |
10.1016/j.celrep.2018.05.043 |
dc.contributor.school |
Tækni- og verkfræðideild (HR) |
dc.contributor.school |
School of Science and Engineering (RU) |