POGZ Is Required for Silencing Mouse Embryonic β-like Hemoglobin and Human Fetal Hemoglobin Expression
Year: 2018
Type: article
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.
Source: Cell Reports
Authors: Bjorg Gudmundsdottir, Kristbjorn O. Gudmundsson, Kimberly D. Klarmann, Satyendra K. Singh, Lei Sun, Shweta Singh, Yang Du, Vincenzo Coppola, Luke Stockwin, Nhu Nguyen, Lino Tessarollo, Leifur Thorsteinsson, Olafur E. Sigurjonsson, Sveinn Gudmundsson, Thorunn Rafnar, John F. Tisdale, Jonathan R. Keller
Institutions: Frederick National Laboratory for Cancer Research, National Cancer Institute, Center for Cancer Research, Leidos Biomedical Research Inc. (United States), Uniformed Services University of the Health Sciences, The Ohio State University Wexner Medical Center, The Ohio State University, National University Hospital of Iceland, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Heart, Lung, and Blood Institute
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: U.S. Department of Health and Human Services, Frederick National Laboratory for Cancer Research, National Institutes of Health, Uniformed Services University of the Health Sciences, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases
OpenAlex ID: W2808024423