The condensation of chromatin in apoptotic thymocytes shows a specific structural change.
Chromatin condensation and DNA cleavage at internucleosomal sites have been recognized early as hallmarks of apoptosis, and it has been suggested that extensive DNA chain scission could directly result in the formation of dense chromatin bodies. Here we have shown that no causal relationship exists between DNA degradation and chromatin condensation in glucocorticoid-induced thymocyte apoptosis. The chromatin rearrangement occurred independent of as well as prior to DNA cleavage and involved a specific conformational change at the nucleosome level. In the early stages of the process, the core particles appeared to be tightly packed face-to-face in smooth 11-nm filaments that progressively folded to generate a closely woven network. The network finally collapsed, producing dense apoptotic bodies. Since trypsin digestion relaxed condensed chromatin and histone H4 underwent appreciable deacetylation in the apoptotic cell, we suggest that changes in the DNA-histone interactions represented a major modulating factor of condensation.
Allera
C
C
Istituto di Studi Chimico-Fisici di Macromolecole Sintetiche e Naturali, Via De Marini, 6 "Torre di Francia," 16146 Genoa, Italy.
Lazzarini
G
G
Patrone
E
E
Alberti
I
I
Barboro
P
P
Sanna
P
P
Melchiori
A
A
Parodi
S
S
Balbi
C
C
D000818:Animals; D017209:Apoptosis; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure*; D004247:DNA / Q000187:drug effects / Q000648:ultrastructure*; D005938:Glucocorticoids / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D008776:Methylprednisolone Hemisuccinate / Q000494:pharmacology; D008854:Microscopy, Electron; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*
D002843:Chromatin; D005938:Glucocorticoids; D006657:Histones; D009707:Nucleosomes; D008776:Methylprednisolone Hemisuccinate; D004247:DNA