Targeting the epigenome: effects of epigenetic treatment strategies on genomic stability in healthy human cells

Epigenetic treatment concepts have long been ascribed as being tumour-selective. Over the last decade, it has become evident that epigenetic mechanisms are essential for a wide range of intracellular functions in healthy cells as well. Evaluation of possible side-effects and their underlying mechanisms in healthy human cells is necessary in order to improve not only patient safety, but also to support future drug development. Since epigenetic regulation directly interacts with genomic and chromosomal packaging density, increasing genomic instability may be a result subsequent to drug-induced epigenetic modifications. This review highlights past and current research efforts on the influence of epigenetic modification on genomic stability in healthy human cells

Chromosomal evidence for a polytypic structure of Arvicanthis niloticus (Rodentia, Muridae)

L'analyse du marquage chromosomique en bande R- et C- d'#Arvicanthis niloticus# en provenance de cinq localités d'Afrique (Egypte, Sénégal, Burkina Faso, Mali et République Centrafricaine) a révélé l'existence de trois formes caryotypiquement distinctes. Ces formes nommées dans ce travail ANI-1, ANI-2 et ANI-3 se différencient entre elles par 6 à 8 remaniements de structure : translocation réciproque, translocations Robertsoniennes et inversions péricentriques. En outre, il existe des différences dans la quantité d'hétérochromatine. Les données obtenues montrent que ces formes, isolées cytogénétiquement représentent trois espèces différentes, et que la révision taxonomique approfondie du genre #Arvicanthis# est nécessaire. (Résumé d'auteur

Delayed and incomplete reprogramming of chromosome methylation patterns in bovine cloned embryos

AbstractFull-term development has now been achieved in several mammalian species by transfer of somatic nuclei into enucleated oocytes [1, 2]. Although a high proportion of such reconstructed embryos can evolve until the blastocyst stage, only a few percent develop into live offspring, which often exhibit developmental abnormalities [3, 4]. Regulatory epigenetic markers such as DNA methylation are imposed on embryonic cells as normal development proceeds, creating differentiated cell states. Cloned embryos require the erasure of their somatic epigenetic markers so as to regain a totipotent state [5]. Here we report on differences in the dynamics of chromosome methylation between cloned and normal bovine embryos before implantation. We show that cloned embryos fail to reproduce distinguishable parental-chromosome methylation patterns after fusion and maintain their somatic pattern during subsequent stages, mainly by a highly reduced efficiency of the passive demethylation process. Surprisingly, chromosomes appear constantly undermethylated on euchromatin in morulae and blastocysts, while centromeric heterochromatin remains more methylated than that of normal embryos. We propose that the abnormal time-dependent methylation events spanning the preimplantation development of clones may significantly interfere with the epigenetic reprogramming, contributing to the high incidence of physiological anomalies occurring later during pregnancy or after clone birth

BrdU replication patterns demonstrating chromosome homoeologies in two fish species, genus Eigenmannia

The karyotypes of two fish species (genus Eigenmannia) from Brazilian rivers were studied with various chromosome banding techniques. BrdU incorporation appears to be the most powerful method for identifying chromosome homoeologies between karyotypes. It also demonstrates asymmetrical hcterochro-matic segments, suggesting an uneven distribution of A-T base pairs in the two DNA strands. In one of these species, males differ from females by the acquisition of a Robertsonian translocation, resulting in a loss of a heterochromatic segment, which may be related to sex differentiation. © 1988 S. Karger AG. Basel.Departamento de Biologia, Instituto de Biociências, Universidade de São Paulo, São PauloStructure et Mutagenèse Chromosomiques, Institut Curie, Section de Biologic, ParisIBBMA-Universidadc Esladual Paulista “Julio de Mesquita Filho”, Botucatu. São PauloIBBMA-Universidadc Esladual Paulista “Julio de Mesquita Filho”, Botucatu. São Paul

Localization of 5-methylcytosine in metaphase chromosomes of diploid and triploid pacu fish, Piaractus mesopotamicus (Pisces, Characiformes)

The distribution of 5-methylcytosine (5-MeC) was investigated in fish chromosomes by indirect immunofluorescence using a highly specific 5-MeC monoclonal antibody. Diploid and artificially produced triploid specimens of the pacu fish, Piaractus mesopotamicus, were analyzed. The strong immunofluorescent signals were coincident with the heterochromatic regions of both diploids and triploids in a pattern that matched the C-banding pattern. In the euchromatin, heterogeneous labeling was observed along the chromatids. The weakness of this labeling hindered comparison of the fluorescence labeling of homologous chromosomes from diploid and triploid individuals. However, no striking differences were observed. The possibility that the euchromatin labeling by the 5-MeC antibody is related to the occurrence of mildly repetitive sequences in the genome of Piaractus is discussed.Departamento de Biologia Instituto de Biociências Universidade de São Paulo, São PauloU 383 INSERM Hôpital Necker-Enfants Malades, ParisDepartamento de Morfologia Instituto de Biociências UNESP, BotucatuInstitut Pasteur CNRS, LyonDepartamento de Biologia Instituto de Biociências USP, Calxa Postal 11.461, 05422-970 São Paulo, SPDepartamento de Morfologia Instituto de Biociências UNESP, Botucat