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Nucleic Acids Research Advance Access originally published online on January 3, 2007
Nucleic Acids Research 2007 35(3):801-811; doi:10.1093/nar/gkl1014
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Nucleic Acids Research, 2007, Vol. 35, No. 3 801-811
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

DNA methylation immediately adjacent to active histone marking does not silence transcription

Arie B. Brinkman, Sebastiaan W. C. Pennings, Georgia G. Braliou, Luc E. G. Rietveld and Hendrik G. Stunnenberg*

Department of Molecular Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University The Netherlands

*To whom correspondence should be addressed at Nijmegen Centre for Molecular Life Sciences 191, PO Box 9191, Nijmegen 6500HB, The Netherlands. Tel: +31 24 3610524; Fax: +31 24 3610520; Email: h.stunnenberg{at}ncmls.ru.nl

Received August 2, 2006. Revised October 27, 2006. Accepted November 1, 2006.

Active promoters generally contain histone H3/H4 hyperacetylation and tri-methylation at H3 lysine 4, whereas repressed promoters are associated with DNA methylation. Here we show that the repressed erythroid-specific carbonic anhydrase II (CAII) promoter has active histone modifications localized around the transcription start, while high levels of CpG methylation are present directly upstream from these active marks. Despite the presence of active histone modifications, the repressed promoter requires hormone-induced activation for efficient preinitiation complex assembly. Transient and positional changes in histone H3/H4 acetylation and local changes in nucleosome density are evident during activation, but the bipartite epigenetic code is stably maintained. Our results suggest that active histone modifications may prevent spreading of CpG methylation towards the promoter and show that repressive DNA methylation immediately adjacent to a promoter does not necessarily repress transcription.

Present addresses: Georgia G. Braliou, Department of Biochemistry, Medical School, University of Thessaly Larissa, Greece Luc E. G. Rietveld, The Netherlands Organization for Health Research and Development Den Haag, The Netherlands


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