This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bowers, S. R.
Right arrow Articles by Cockerill, P. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bowers, S. R.
Right arrow Articles by Cockerill, P. N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2009, p. 1682-1693, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.01411-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Conserved Insulator That Recruits CTCF and Cohesin Exists between the Closely Related but Divergently Regulated Interleukin-3 and Granulocyte-Macrophage Colony-Stimulating Factor Genes{triangledown}

Sarion R. Bowers,1 Fabio Mirabella,1,§ Fernando J. Calero-Nieto,1,{dagger},§ Stephanie Valeaux,1 Suzana Hadjur,2 Euan W. Baxter,1,{ddagger} Matthias Merkenschlager,2 and Peter N. Cockerill1*

Experimental Haematology, Leeds Institute of Molecular Medicine, University of Leeds, St. James's University Hospital, Leeds LS9 7TF, United Kingdom,1 Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College, Du Cane Road, London W12 ONN, United Kingdom2

Received 8 September 2008/ Returned for modification 5 November 2008/ Accepted 9 January 2009

The human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating-factor (GM-CSF, or CSF2) gene cluster arose by duplication of an ancestral gene. Although just 10 kb apart and responsive to the same signals, the IL-3 and GM-CSF genes are nevertheless regulated independently by separate, tissue-specific enhancers. To understand the differential regulation of the IL-3 and GM-CSF genes we have investigated a cluster of three ubiquitous DNase I-hypersensitive sites (DHSs) located between the two genes. We found that each site contains a conserved CTCF consensus sequence, binds CTCF, and recruits the cohesin subunit Rad21 in vivo. The positioning of these sites relative to the IL-3 and GM-CSF genes and their respective enhancers is conserved between human and mouse, suggesting a functional role in the organization of the locus. We found that these sites effectively block functional interactions between the GM-CSF enhancer and either the IL-3 or the GM-CSF promoter in reporter gene assays. These data argue that the regulation of the IL-3 and the GM-CSF promoters depends on the positions of their enhancers relative to the conserved CTCF/cohesin-binding sites. We suggest that one important role of these sites is to enable the independent regulation of the IL-3 and GM-CSF genes.

* Corresponding author. Mailing address: Experimental Haematology, Leeds Institute of Molecular Medicine, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds LS9 7TF, United Kingdom. Phone: 44 113 3438639. Fax: 44 113 3438502. E-mail: p.n.cockerill{at}leeds.ac.uk

{triangledown} Published ahead of print on 21 January 2009.

§ F.M. and F.J.C.-N. contributed equally to this study.

{dagger} Present address: Department of Haematology, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Cambridge, United Kingdom.

{ddagger} Present address: YCR p53 Research Unit, Department of Biology, University of York, York YO10 5DD, United Kingdom.

Molecular and Cellular Biology, April 2009, p. 1682-1693, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.01411-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Molto, E., Fernandez, A., Montoliu, L. (2009). Boundaries in vertebrate genomes: different solutions to adequately insulate gene expression domains. Brief Funct Genomic Proteomic 8: 283-296 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»