This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 Esnault, G.
Right arrow Articles by Mermod, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Esnault, G.
Right arrow Articles by Mermod, N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2009, p. 2409-2418, Vol. 29, No. 9
0270-7306/09/$08.00+0     doi:10.1128/MCB.00779-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Transcription Factor CTF1 Acts as a Chromatin Domain Boundary That Shields Human Telomeric Genes from Silencing{triangledown} ,{dagger}

Germain Esnault,1 Stefano Majocchi,1 Danielle Martinet,2 Nathalie Besuchet-Schmutz,2 Jacques S. Beckmann,2,3 and Nicolas Mermod1*

Institute of Biotechnology, University of Lausanne, Lausanne, Switzerland,1 Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland,2 Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland3

Received 15 May 2008/ Returned for modification 10 June 2008/ Accepted 5 February 2009

Telomeres are associated with chromatin-mediated silencing of genes in their vicinity. However, how epigenetic markers mediate mammalian telomeric silencing and whether specific proteins may counteract this effect are not known. We evaluated the ability of CTF1, a DNA- and histone-binding transcription factor, to prevent transgene silencing at human telomeres. CTF1 was found to protect a gene from silencing when its DNA-binding sites were interposed between the gene and the telomeric extremity, while it did not affect a gene adjacent to the telomere. Protein fusions containing the CTF1 histone-binding domain displayed similar activities, while mutants impaired in their ability to interact with the histone did not. Chromatin immunoprecipitation indicated the propagation of a hypoacetylated histone structure to various extents depending on the telomere. The CTF1 fusion protein was found to recruit the H2A.Z histone variant at the telomeric locus and to restore high histone acetylation levels to the insulated telomeric transgene. Histone lysine trimethylations were also increased on the insulated transgene, indicating that these modifications may mediate expression rather than silencing at human telomeres. Overall, these results indicate that transcription factors can act to delimit chromatin domain boundaries at mammalian telomeres, thereby blocking the propagation of a silent chromatin structure.

* Corresponding author. Mailing address: Institute of Biotechnology, Station 6, 1015 Lausanne, Switzerland. Phone: 41 21 693 6151. Fax: 41 21 693 7610. E-mail: Nicolas.Mermod{at}unil.ch

{triangledown} Published ahead of print on 9 March 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, May 2009, p. 2409-2418, Vol. 29, No. 9
0270-7306/09/$08.00+0     doi:10.1128/MCB.00779-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Plasari, G., Calabrese, A., Dusserre, Y., Gronostajski, R. M., Mcnair, A., Michalik, L., Mermod, N. (2009). Nuclear Factor I-C Links Platelet-Derived Growth Factor and Transforming Growth Factor {beta}1 Signaling to Skin Wound Healing Progression. Mol. Cell. Biol. 29: 6006-6017 [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»