POGZ Is Required for Silencing Mouse Embryonic ß-like Hemoglobin and Human Fetal Hemoglobin Expression.
Cell Rep
; 23(11): 3236-3248, 2018 06 12.
Article
em En
| MEDLINE
| ID: mdl-29898395
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.
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1
Base de dados:
MEDLINE
Assunto principal:
Hemoglobina Fetal
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Transposases
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Globinas beta
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article