Gene positional changes relative to the nuclear substructure correlate with the proliferating status of hepatocytes during liver regeneration.
In the interphase nucleus the DNA of higher eukaryotes is organised in loops anchored to a proteinaceous substructure variously named but commonly known as the nuclear matrix. Important processes of nuclear physiology, such as replication, transcription and processing of primary transcripts, occur at macromolecular complexes located at discrete sites upon the nuclear substructure. The topological relationships between gene sequences located in the DNA loops and the nuclear substructure appear to be non-random, thus posing the question of whether such relationships remain invariant or change after the critical nuclear transitions associated with cell proliferation and tissue regeneration in vivo. The hepatocytes are cells that preserve a proliferating capacity that is readily displayed after partial ablation of the liver, leading to liver regeneration in experimental animals such as the rat. Using this animal model coupled to a recently developed PCR-based method for mapping the position of specific DNA sequences relative to the nuclear substructure, we provide evidence that transient changes in the topological relationships between specific genes and the nuclear substructure occur during liver regeneration and that such changes correlate with the actual proliferating status of the cells, thus suggesting that specific transitions in the higher-order DNA structure are characteristic of the quiescent (G0) and replicating (S) phases of the cell cycle in vivo.
Laboratorio de Biología Molecular, Facultad de Medicina, Universidad Autónoma del Estado de México, Apartado Postal 428, C.P. 50000, Toluca, Edo. Méx., México.
Apolinar
A
Maya-Mendoza
Rolando
R
Hernández-Muñoz
Patricio
P
Gariglio
Armando
A
Aranda-Anzaldo
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005796:Genes / Q000502:physiology*; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D007700:Kinetics; D008115:Liver Regeneration; D008297:Male; D009068:Movement; D015530:Nuclear Matrix / Q000378:metabolism; D009690:Nucleic Acid Conformation; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D016192:Resting Phase, Cell Cycle; D016196:S Phase
D004247:DNA