POGZ Is Required for Silencing Mouse Embryonic β-like Hemoglobin and Human Fetal Hemoglobin Expression

2.50
Hdl Handle:
http://hdl.handle.net/2336/620639
Title:
POGZ Is Required for Silencing Mouse Embryonic β-like Hemoglobin and Human Fetal Hemoglobin Expression
Authors:
Gudmundsdottir, Bjorg; Gudmundsson, Kristbjorn O.; Klarmann, Kimberly D.; Singh, Satyendra K.; Sun, Lei; Singh, Shweta; Du, Yang; Coppola, Vincenzo; Stockwin, Luke; Nguyen, Nhu; Tessarollo, Lino; Thorsteinsson, Leifur; Sigurjonsson, Olafur E.; Gudmundsson, Sveinn; Rafnar, Thorunn; Tisdale, John F.; Keller, Jonathan R.
Citation:
POGZ Is Required for Silencing Mouse Embryonic β-like Hemoglobin and Human Fetal Hemoglobin Expression 2018, 23 (11):3236 Cell Reports
Issue Date:
Jun-2018
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.
Description:
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files
Additional Links:
https://linkinghub.elsevier.com/retrieve/pii/S2211124718307897
Rights:
Archived with thanks to Cell Reports

Full metadata record

DC FieldValue Language
dc.contributor.authorGudmundsdottir, Bjorgen
dc.contributor.authorGudmundsson, Kristbjorn O.en
dc.contributor.authorKlarmann, Kimberly D.en
dc.contributor.authorSingh, Satyendra K.en
dc.contributor.authorSun, Leien
dc.contributor.authorSingh, Shwetaen
dc.contributor.authorDu, Yangen
dc.contributor.authorCoppola, Vincenzoen
dc.contributor.authorStockwin, Lukeen
dc.contributor.authorNguyen, Nhuen
dc.contributor.authorTessarollo, Linoen
dc.contributor.authorThorsteinsson, Leifuren
dc.contributor.authorSigurjonsson, Olafur E.en
dc.contributor.authorGudmundsson, Sveinnen
dc.contributor.authorRafnar, Thorunnen
dc.contributor.authorTisdale, John F.en
dc.contributor.authorKeller, Jonathan R.en
dc.date.accessioned2018-07-05T11:28:01Z-
dc.date.available2018-07-05T11:28:01Z-
dc.date.issued2018-06-
dc.date.submitted2018-
dc.identifier.citationPOGZ Is Required for Silencing Mouse Embryonic β-like Hemoglobin and Human Fetal Hemoglobin Expression 2018, 23 (11):3236 Cell Reportsen
dc.identifier.issn22111247-
dc.identifier.doi10.1016/j.celrep.2018.05.043-
dc.identifier.urihttp://hdl.handle.net/2336/620639-
dc.descriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Filesen
dc.description.abstractFetal 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.en
dc.description.sponsorshipFrederick National Laboratory for Cancer Research, NIH intramural research program of the NHLBI, NIH intramural research program of the NIDDK, NIH USUHSen
dc.language.isoenen
dc.publisherCell Pressen
dc.relation.urlhttps://linkinghub.elsevier.com/retrieve/pii/S2211124718307897en
dc.rightsArchived with thanks to Cell Reportsen
dc.subjectPrótínen
dc.subjectBAB12en
dc.subject.meshFetal Hemoglobinen
dc.subject.meshGlobinsen
dc.titlePOGZ Is Required for Silencing Mouse Embryonic β-like Hemoglobin and Human Fetal Hemoglobin Expressionen
dc.typeArticleen
dc.contributor.department[ 1 ] NCI, Mouse Canc Genet Program, Ctr Canc Res, Bldg 560-12-70,1050 Boyles St, Frederick, MD 21702 USA Show more [ 2 ] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Basic Res Program, Bldg 560-32-31D,1050 Boyles St, Frederick, MD 21702 USA Show more [ 3 ] Uniformed Serv Univ Hlth Sci, Dept Pediat, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA Show more [ 4 ] Ohio State Univ, Wexner Med Ctr, 460 West 12th Ave, Columbus, OH 43210 USA Show more [ 5 ] NCI, Drug Mechanisms Grp, Dev Therapeut Program, Leidos Biomed Res Inc, Frederick, MD 21702 USA Show more [ 6 ] Landspitali Univ Hosp, Blood Bank, Snorrabraut 60, IS-105 Reykjavik, Iceland [ 7 ] Iceland Genom Corp, Snorrabraut 60, IS-105 Reykjavik, Iceland Show more [ 8 ] NIDDK, Mol & Clin Hematol Branch, NHLBI, NIH, Bethesda, MD 20814 USA Show more [ 9 ] NHLBI, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N112, Bethesda, MD 20814 USAen
dc.identifier.journalCell Reportsen
dc.rights.accessOpen Access - Opinn aðganguren
dc.departmentcodeBAB12-
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