Nucleic Acids Research Advance Access originally published online on May 3, 2007
Nucleic Acids Research 2007 35(10):3431-3441; doi:10.1093/nar/gkm214
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Nucleic Acids Research, 2007, Vol. 35, No. 10 3431-3441
© 2007 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 |
Transcription-coupled deposition of histone modifications during MHC class II gene activation
Department of Pathology and Immunology, University of Geneva Medical School, 1 rue Michel-Servet, CH-1211, Geneva, Switzerland
*To whom correspondence should be addressed. Tel: +41 22 379 56 66; Fax: +41 22 379 57 46; Email: walter.reith{at}medecine.unige.ch
Received November 3, 2006. Revised March 20, 2007. Accepted March 27, 2007.
Posttranslational histone modifications associated with actively expressed genes are generally believed to be introduced primarily by histone-modifying enzymes that are recruited by transcription factors or their associated co-activators. We have performed a comprehensive spatial and temporal analyses of the histone modifications that are deposited upon activation of the MHC class II gene HLA-DRA by the co-activator CIITA. We find that transcription-associated histone modifications are introduced during two sequential phases. The first phase precedes transcription initiation and is characterized exclusively by a rapid increase in histone H4 acetylation over a large upstream domain. All other modifications examined, including the acetylation and methylation of several residues in histone H3, are restricted to short regions situated at or within the 5' end of the gene and are established during a second phase that is concomitant with ongoing transcription. This second phase is completely abrogated when elongation by RNA polymerase II is blocked. These results provide strong evidence that transcription elongation can play a decisive role in the deposition of histone modification patterns associated with inducible gene activation.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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