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Molecular and Cellular Biology, March 2009, p. 1526-1537, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01523-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Ikaros and GATA-1 Combinatorial Effect Is Required for Silencing of Human {gamma}-Globin Genes{triangledown}

Stefania Bottardi,1,{dagger} Julie Ross,1,{dagger} Vincent Bourgoin,1 Nasser Fotouhi-Ardakani,1 El Bachir Affar,1 Marie Trudel,2 and Eric Milot1,3*

Maisonneuve Rosemont Hospital Research Center, Maisonneuve-Rosemont Hospital and Faculty of Medicine, University of Montreal, 5415 Boulevard l'Assomption, Montreal, Quebec H1T 2M4, Canada,1 Institut de Recherches Cliniques de Montreal and Faculty of Medicine, University of Montreal, 110 Avenue des Pins Ouest, Montreal, Quebec H2W 1R7, Canada,2 Institute for Research in Immunology and Cancer, University of Montreal, C.P. Succursale Centre-Ville, Montreal, Quebec H3T 3J7, Canada3

Received 30 September 2008/ Returned for modification 19 October 2008/ Accepted 19 December 2008

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 β-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 β-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.

* Corresponding author. Mailing address: Maisonneuve Rosemont Hospital Research Center, Maisonneuve-Rosemont Hospital and Faculty of Medicine, University of Montreal, 5415 Boulevard l'Assomption, Montreal, Quebec H1T 2M4, Canada. Phone: (514) 252-3551. Fax: (514) 252-3430. E-mail: e.milot.1{at}umontreal.ca

{triangledown} Published ahead of print on 29 December 2008.

{dagger} S.B. and J.R. contributed equally to this study.

Molecular and Cellular Biology, March 2009, p. 1526-1537, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01523-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Umetsu, S. E., Winandy, S. (2009). Ikaros Is a Regulator of Il10 Expression in CD4+ T Cells. J. Immunol. 183: 5518-5525 [Abstract] [Full Text]  
  • Palstra, R.-J. T. S. (2009). Close encounters of the 3C kind: long-range chromatin interactions and transcriptional regulation. Brief Funct Genomic Proteomic 0: elp016v2-elp016 [Abstract] [Full Text]  


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