HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 19, 13540-13547, May 12, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/19/13540    most recent M601136200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Boix-Chornet, M. Articles by Ballestar, E. Search for Related Content PubMed PubMed Citation Articles by Boix-Chornet, M. Articles by Ballestar, E. Social Bookmarking                      What's this?

Release of Hypoacetylated and Trimethylated Histone H4 Is an Epigenetic Marker of Early Apoptosis^*

Manuel Boix-Chornet¹, Mario F. Fraga, Ana Villar-Garea, Rosalia Caballero, Jesus Espada, Antonio Nuñez^¶, Juan Casado^¶, Cristina Largo^||, J. Ignacio Casal^¶, Juan C. Cigudosa^||, Luis Franco^**, Manel Esteller², and Esteban Ballestar³

From the Cancer Epigenetics Laboratory, Molecular Pathology Programme, ^¶Protein Technology Unit, Biotechnology Programme, and ^||Molecular Cytogenetics Group, Human Cancer Genetics Programme, Spanish National Cancer Centre, 28029 Madrid, Laboratory 14, Cancer Research Center, University of Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, and ^**Department of Biochemistry and Molecular Biology, University of Valencia, 46100 Valencia, Spain

Nuclear events such as chromatin condensation, DNA cleavage at internucleosomal sites, and histone release from chromatin are recognized as hallmarks of apoptosis. However, there is no complete understanding of the molecular events underlying these changes. It is likely that epigenetic changes such as DNA methylation and histone modifications that are involved in chromatin dynamics and structure are also involved in the nuclear events described. In this report we have shown that apoptosis is associated with global DNA hypomethylation and histone deacetylation events in leukemia cells. Most importantly, we have observed a particular epigenetic signature for early apoptosis defined by a release of hypoacetylated and trimethylated histone H4 and internucleosomal fragmented DNA that is hypermethylated and originates from perinuclear heterochromatin. These findings provide one of the first links between apoptotic nuclear events and epigenetic markers.

Received for publication, February 6, 2006 , and in revised form, March 7, 2006.

^* This work was supported by Grants SAF 2001-0059, BFU2004-02073/BMC and Ramon y Cajal Programme (MCYT), and GR/SAL/0224/2004 (Government of Madrid). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1.

¹ Present address: Section of Haematological Oncology, Inst. of Cancer Research, London, UK.

² To whom correspondence may be addressed. E-mail: mesteller{at}cnio.es. ³ To whom correspondence may be addressed: Cancer Epigenetics Laboratory, Molecular Pathology Programme, Spanish National Cancer Centre, Melchor Fernández Almagro 3, 28029 Madrid, Spain. Tel.: 34-912-246-900; Fax: 34-912-246-923. E-mail: eballestar{at}cnio.es.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?