Zfp281 (ZBP-99) plays a functionally redundant role with Zfp148 (ZBP-89) during erythroid development
Name
Woo et al MS Ver 3 Blood Advances.pdf
Description
Accepted version
Size
5.28 MB
Format
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Checksum (MD5)
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Author(s)
Woo, Andrew J.
Patry, Chelsea-Ann A.
Ghamari, Alireza
Pregernig, Gabriela
Yuan, Daniel
Zheng, Kangni
Piers, Taylor
Hibbs, Moira
Li, Ji
Fidalgo, Miguel
Date Issued
August 2019
Journal
Blood Advances
Publisher
American Society of Hematology
Citation
Woo, Andrew J. et al. "Zfp281 (ZBP-99) plays a functionally redundant role with Zfp148 (ZBP-89) during erythroid development." Red Cells, Iron, and Erythropoiesis 3, 16 (August 2019): 2499–2511 © 2019 The American Society of Hematology
Version
Author's final manuscript
Abstract
Erythroid maturation requires the concerted action of a core set of transcription factors. Wepreviously identified the Krüppel-type zinc finger transcription factor Zfp148 (also called ZBP-89) as an interacting partner of the master erythroid transcription factor GATA1. Here we report the conditional knockout of Zfp148 in mice. Global loss of Zfp148 results in perinatal lethality from nonhematologic causes. Selective Zfp148 loss within the hematopoietic system results in a mild microcytic and hypochromic anemia, mildly impaired erythroid maturation, and delayed recovery from phenylhydrazine-induced hemolysis. Based on the mild erythroid phenotype of these mice compared with GATA1- deficient mice, we hypothesized that additional factor(s) may complement Zfp148 function during erythropoiesis. We show that Zfp281 (also called ZBP-99), another member of the Zfp148 transcription factor family, is highly expressed in murine and human erythroid cells. Zfp281 knockdown by itself results in partial erythroid defects. However, combined deficiency of Zfp148 and Zfp281 causes a marked erythroid maturation block. Zfp281 physically associates with GATA1, occupies many common chromatin sites with GATA1 and Zfp148, and regulates a common set of genes required for erythroid cell differentiation. These findings uncover a previously unknown role for Zfp281 in erythroid development and suggest that it functionally overlaps with that of Zfp148 during erythropoiesis.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1182/bloodadvances.2018030551
