Dataset Information

Eos negatively regulates human ?-globin gene transcription during erythroid differentiation.

ABSTRACT:

Background

Human globin gene expression is precisely regulated by a complicated network of transcription factors and chromatin modifying activities during development and erythropoiesis. Eos (Ikaros family zinc finger 4, IKZF4), a member of the zinc finger transcription factor Ikaros family, plays a pivotal role as a repressor of gene expression. The aim of this study was to examine the role of Eos in globin gene regulation.

Methodology/principal findings

Western blot and quantitative real-time PCR detected a gradual decrease in Eos expression during erythroid differentiation of hemin-induced K562 cells and Epo-induced CD34+ hematopoietic stem/progenitor cells (HPCs). DNA transfection and lentivirus-mediated gene transfer demonstrated that the enforced expression of Eos significantly represses the expression of ?-globin, but not other globin genes, in K562 cells and CD34+ HPCs. Consistent with a direct role of Eos in globin gene regulation, chromatin immunoprecipitaion and dual-luciferase reporter assays identified three discrete sites located in the DNase I hypersensitivity site 3 (HS3) of the ?-globin locus control region (LCR), the promoter regions of the G?- and A?- globin genes, as functional binding sites of Eos protein. A chromosome conformation capture (3C) assay indicated that Eos may repress the interaction between the LCR and the ?-globin gene promoter. In addition, erythroid differentiation was inhibited by enforced expression of Eos in K562 cells and CD34+ HPCs.

Conclusions/significance

Our results demonstrate that Eos plays an important role in the transcriptional regulation of the ?-globin gene during erythroid differentiation.

SUBMITTER: Yu HC

PROVIDER: S-EPMC3145782 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

Eos negatively regulates human γ-globin gene transcription during erythroid differentiation.

Yu Hai-Chuan HC Zhao Hua-Lu HL Wu Zhi-Kui ZK Zhang Jun-Wu JW

PloS one 20110728 7

<h4>Background</h4>Human globin gene expression is precisely regulated by a complicated network of transcription factors and chromatin modifying activities during development and erythropoiesis. Eos (Ikaros family zinc finger 4, IKZF4), a member of the zinc finger transcription factor Ikaros family, plays a pivotal role as a repressor of gene expression. The aim of this study was to examine the role of Eos in globin gene regulation.<h4>Methodology/principal findings</h4>Western blot and quantita ...[more]

PMID: 21829552

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