Zfp281 (ZBP-99) plays a functionally redundant role with Zfp148 (ZBP-89) during erythroid development

Andrew Woo, Chelsea-Ann A Patry, Alireza Ghamari, Gabriela Pregernig, Daniel Yuan, Kangni Zheng, Taylor Piers, Moira Hibbs, Ji Kevin Li, Miguel Fidalgo, Jenny Y Wang, Joo-Hyeon Lee, Peter Leedman, Jianlong Wang, Ernest Fraenkel, Alan B Cantor

Research output: Contribution to journalArticle

Abstract

Erythroid maturation requires the concerted action of a core set of transcription factors. We previously 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.

Original languageEnglish
Pages (from-to)2499-2511
Number of pages13
JournalBlood advances
Volume3
Issue number16
DOIs
Publication statusPublished - 27 Aug 2019

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Erythroid Cells
Transcription Factors
Erythropoiesis
GATA1 Transcription Factor
Hematopoietic System
Zinc Fingers
Hemolysis
Chromatin
Cell Differentiation
Phenotype
Genes
phenylhydrazine
Hypochromic microcytic Anemia

Cite this

Woo, A., Patry, C-A. A., Ghamari, A., Pregernig, G., Yuan, D., Zheng, K., ... Cantor, A. B. (2019). Zfp281 (ZBP-99) plays a functionally redundant role with Zfp148 (ZBP-89) during erythroid development. Blood advances, 3(16), 2499-2511. https://doi.org/10.1182/bloodadvances.2018030551
Woo, Andrew ; Patry, Chelsea-Ann A ; Ghamari, Alireza ; Pregernig, Gabriela ; Yuan, Daniel ; Zheng, Kangni ; Piers, Taylor ; Hibbs, Moira ; Li, Ji Kevin ; Fidalgo, Miguel ; Wang, Jenny Y ; Lee, Joo-Hyeon ; Leedman, Peter ; Wang, Jianlong ; Fraenkel, Ernest ; Cantor, Alan B. / Zfp281 (ZBP-99) plays a functionally redundant role with Zfp148 (ZBP-89) during erythroid development. In: Blood advances. 2019 ; Vol. 3, No. 16. pp. 2499-2511.
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title = "Zfp281 (ZBP-99) plays a functionally redundant role with Zfp148 (ZBP-89) during erythroid development",
abstract = "Erythroid maturation requires the concerted action of a core set of transcription factors. We previously identified the Kr{\"u}ppel-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.",
author = "Andrew Woo and Patry, {Chelsea-Ann A} and Alireza Ghamari and Gabriela Pregernig and Daniel Yuan and Kangni Zheng and Taylor Piers and Moira Hibbs and Li, {Ji Kevin} and Miguel Fidalgo and Wang, {Jenny Y} and Joo-Hyeon Lee and Peter Leedman and Jianlong Wang and Ernest Fraenkel and Cantor, {Alan B}",
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Woo, A, Patry, C-AA, Ghamari, A, Pregernig, G, Yuan, D, Zheng, K, Piers, T, Hibbs, M, Li, JK, Fidalgo, M, Wang, JY, Lee, J-H, Leedman, P, Wang, J, Fraenkel, E & Cantor, AB 2019, 'Zfp281 (ZBP-99) plays a functionally redundant role with Zfp148 (ZBP-89) during erythroid development' Blood advances, vol. 3, no. 16, pp. 2499-2511. https://doi.org/10.1182/bloodadvances.2018030551

Zfp281 (ZBP-99) plays a functionally redundant role with Zfp148 (ZBP-89) during erythroid development. / Woo, Andrew; Patry, Chelsea-Ann A; Ghamari, Alireza; Pregernig, Gabriela; Yuan, Daniel; Zheng, Kangni; Piers, Taylor; Hibbs, Moira; Li, Ji Kevin; Fidalgo, Miguel; Wang, Jenny Y; Lee, Joo-Hyeon; Leedman, Peter; Wang, Jianlong; Fraenkel, Ernest; Cantor, Alan B.

In: Blood advances, Vol. 3, No. 16, 27.08.2019, p. 2499-2511.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Zfp281 (ZBP-99) plays a functionally redundant role with Zfp148 (ZBP-89) during erythroid development

AU - Woo, Andrew

AU - Patry, Chelsea-Ann A

AU - Ghamari, Alireza

AU - Pregernig, Gabriela

AU - Yuan, Daniel

AU - Zheng, Kangni

AU - Piers, Taylor

AU - Hibbs, Moira

AU - Li, Ji Kevin

AU - Fidalgo, Miguel

AU - Wang, Jenny Y

AU - Lee, Joo-Hyeon

AU - Leedman, Peter

AU - Wang, Jianlong

AU - Fraenkel, Ernest

AU - Cantor, Alan B

PY - 2019/8/27

Y1 - 2019/8/27

N2 - Erythroid maturation requires the concerted action of a core set of transcription factors. We previously 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.

AB - Erythroid maturation requires the concerted action of a core set of transcription factors. We previously 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.

U2 - 10.1182/bloodadvances.2018030551

DO - 10.1182/bloodadvances.2018030551

M3 - Article

VL - 3

SP - 2499

EP - 2511

JO - Blood advances

JF - Blood advances

SN - 2473-9529

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