Release of hypoacetylated and trimethylated histone H4 is an epigenetic marker of early apoptosis.
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.
Cancer Epigenetics Laboratory, Molecular Pathology Programme.
Manuel
M
Boix-Chornet
Cancer Epigenetics Laboratory, Molecular Pathology Programme.
Mario F
MF
Fraga
Cancer Epigenetics Laboratory, Molecular Pathology Programme.
Ana
A
Villar-Garea
Laboratory 14, Cancer Research Center, University of Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
Rosalia
R
Caballero
Cancer Epigenetics Laboratory, Molecular Pathology Programme.
Jesus
J
Espada
Protein Technology Unit, Biotechnology Programme, 28029 Madrid, Spain.
Antonio
A
Nuñez
Protein Technology Unit, Biotechnology Programme, 28029 Madrid, Spain.
Juan
J
Casado
Molecular Cytogenetics Group, Human Cancer Genetics Programme, Spanish National Cancer Centre, 28029 Madrid, Spain.
Cristina
C
Largo
Protein Technology Unit, Biotechnology Programme, 28029 Madrid, Spain.
J Ignacio
JI
Casal
Molecular Cytogenetics Group, Human Cancer Genetics Programme, Spanish National Cancer Centre, 28029 Madrid, Spain.
Juan C
JC
Cigudosa
Department of Biochemistry and Molecular Biology, University of Valencia, 46100 Valencia, Spain.
Luis
L
Franco
Cancer Epigenetics Laboratory, Molecular Pathology Programme. Electronic address: mesteller@cnio.es.
Manel
M
Esteller
Cancer Epigenetics Laboratory, Molecular Pathology Programme. Electronic address: eballestar@cnio.es.
Esteban
E
Ballestar
D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation; D018922:HL-60 Cells; D006570:Heterochromatin / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells
D015415:Biomarkers; D006570:Heterochromatin; D006657:Histones; D004247:DNA