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

  1. Author:
    Gudmundsdottir, Bjorg
    Gudmundsson, Kristbjorn O
    Klarmann, Kimberly
    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

  2. Author Address

    Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute at Frederick, Bldg. 560/12-70, 1050 Boyles Street, Frederick, MD 21702, USA., Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute at Frederick, Bldg. 560/12-70, 1050 Boyles Street, Frederick, MD 21702, USA; Basic Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Bldg. 560/32-31D, 1050 Boyles Street, Frederick, MD 21702, USA., Department of Pediatrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA., Wexner Medical Center, Ohio State University, 460 West 12(th)Avenue, Columbus, OH 43210, USA., Drug Mechanisms Group, Developmental Therapeutics Program, Leidos Biomedical Research, Inc., National Cancer Institute at Frederick, Frederick, MD 21702, USA., The Blood Bank, Landspitali University Hospital, Snorrabraut 60, 105 Reykjavik, Iceland., Iceland Genomics Corporation, Snorrabraut 60, 105 Reykjavik, Iceland., Molecular and Clinical Hematology Branch, NHLBI/NIDDK, NIH, Bethesda, MD 20814, USA., Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute at Frederick, Bldg. 560/12-70, 1050 Boyles Street, Frederick, MD 21702, USA; Basic Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Bldg. 560/32-31D, 1050 Boyles Street, Frederick, MD 21702, USA. Electronic address: kellerjo@mail.nih.gov.,
    1. Year: 2018
    2. Date: Jun 12
  2. Journal: Cell Reports
    1. 23
    2. 11
    3. Pages: 3236-3248
  4. Type of Article: Article
  5. ISSN: 2211-1247
  1. 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 ß-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 ß-like globin expression without affecting erythroid development. POGZ binds to the Bcl11a promoter and erythroid-specific intragenic regulatory regions. Pogz+/- mice show elevated embryonic ß-like globin expression, suggesting that partial reduction of Pogz expression results in persistence of embryonic ß-like globin expression. Knockdown of POGZ in primary human CD34+ progenitor cell-derived erythroblasts reduces BCL11A expression, a known repressor of embryonic ß-like globin expression, and increases fetal hemoglobin expression. These findings are significant, since new therapeutic targets and strategies are needed to treat ß-globin disorders. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2018.05.043
  3. PMID: 29898395
  4. View record in Web of Science®
  5. WOS: 000435196500011
  6. PII : S2211-1247(18)30789-7

Library Notes

  1. Fiscal Year: FY2017-2018
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