| First Author | Gudmundsdottir B | Year | 2018 |
| Journal | Cell Rep | Volume | 23 |
| Issue | 11 | Pages | 3236-3248 |
| PubMed ID | 29898395 | Mgi Jnum | J:271614 |
| Mgi Id | MGI:6278314 | Doi | 10.1016/j.celrep.2018.05.043 |
| Citation | Gudmundsdottir B, et al. (2018) POGZ Is Required for Silencing Mouse Embryonic beta-like Hemoglobin and Human Fetal Hemoglobin Expression. Cell Rep 23(11):3236-3248 |
| abstractText | 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 beta-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 beta-like globin expression without affecting erythroid development. POGZ binds to the Bcl11a promoter and erythroid-specific intragenic regulatory regions. Pogz(+/-) mice show elevated embryonic beta-like globin expression, suggesting that partial reduction of Pogz expression results in persistence of embryonic beta-like globin expression. Knockdown of POGZ in primary human CD34(+) progenitor cell-derived erythroblasts reduces BCL11A expression, a known repressor of embryonic beta-like globin expression, and increases fetal hemoglobin expression. These findings are significant, since new therapeutic targets and strategies are needed to treat beta-globin disorders. |
