The Mouse KLF1 Nan Variant Impairs Nuclear Condensation and Erythroid Maturation

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2019 Mar 29

PMID 30921348

Citations 8

Authors

Ileana Cantu

Harmen J G van de Werken

Nynke Gillemans

Ralph Stadhouders

Steven Heshusius

Alex Maas

Fatemehsadat Esteghamat

Zeliha Ozgur

Wilfred F J van IJcken

Frank Grosveld

Marieke von Lindern

Sjaak Philipsen

Thamar B van Dijk

Affiliations

Soon will be listed here.

Abstract

Krüppel-like factor 1 (KLF1) is an essential transcription factor for erythroid development, as demonstrated by Klf1 knockout mice which die around E14 due to severe anemia. In humans, >140 KLF1 variants, causing different erythroid phenotypes, have been described. The KLF1 Nan variant, a single amino acid substitution (p.E339D) in the DNA binding domain, causes hemolytic anemia and is dominant over wildtype KLF1. Here we describe the effects of the KLF1 Nan variant during fetal development. We show that Nan embryos have defects in erythroid maturation. RNA-sequencing of the KLF1 Nan fetal liver cells revealed that Exportin 7 (Xpo7) was among the 782 deregulated genes. This nuclear exportin is implicated in terminal erythroid differentiation; in particular it is involved in nuclear condensation. Indeed, KLF1 Nan fetal liver cells had larger nuclei and reduced chromatin condensation. Knockdown of XPO7 in wildtype erythroid cells caused a similar phenotype. We propose that reduced expression of XPO7 is partially responsible for the erythroid defects observed in KLF1 Nan erythroid cells.

Citing Articles

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An In Vivo Model for Elucidating the Role of an Erythroid-Specific Isoform of Nuclear Export Protein Exportin 7 (Xpo7) in Murine Erythropoiesis.

Modepalli S, Martinez-Morilla S, Venkatesan S, Fasano J, Paulsen K, Gorlich D Exp Hematol. 2022; 114:22-32.

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Epigenetic and Transcriptional Control of Erythropoiesis.

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