Ikaros and GATA-1 combinatorial effect is required for silencing of human gamma-globin genes.

Abstract:

:During development and erythropoiesis, globin gene expression is finely modulated through an important network of transcription factors and chromatin modifying activities. In this report we provide in vivo evidence that endogenous Ikaros is recruited to the human beta-globin locus and targets the histone deacetylase HDAC1 and the chromatin remodeling protein Mi-2 to the human gamma-gene promoters, thereby contributing to gamma-globin gene silencing at the time of the gamma- to beta-globin gene transcriptional switch. We show for the first time that Ikaros interacts with GATA-1 and enhances the binding of the latter to different regulatory regions across the locus. Consistent with these results, we show that the combinatorial effect of Ikaros and GATA-1 impairs close proximity between the locus control region and the human gamma-globin genes. Since the absence of Ikaros also affects GATA-1 recruitment to GATA-2 promoter, we propose that the combinatorial effect of Ikaros and GATA-1 is not restricted to globin gene regulation.

journal_name

Mol Cell Biol

authors

Bottardi S,Ross J,Bourgoin V,Fotouhi-Ardakani N,Affar el B,Trudel M,Milot E

doi

10.1128/MCB.01523-08

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

1526-37

issue

6

eissn

0270-7306

issn

1098-5549

pii

MCB.01523-08

journal_volume

29

pub_type

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