Hypomethylation of classical satellite DNA and chromosome instability in lymphoblastoid cell lines.
To determine possible relationships between DNA hypomethylation and chromosome instability, human lymphoblastoid cell lines from different genetic constitutions were studied with regard to 1) uncoiling and rearrangements, which preferentially affect the heterochromatic segments of chromosomes 1 and 16; 2) the methylation status of the tandemly repetitive sequences (classical satellite and alphoid DNAs) from chromosomes 1 and 16, and of the L1Hs interspersed repetitive sequences. The methylation status largely varied from cell line to cell line, but for a given cell line, the degree of methylation was similar for all the repetitive DNAs studied. Two cell lines, one obtained from a Fanconi anemia patient and the other from an ataxia telangiectasia patient were found to be heavily hypomethylated. The heterochromatic segments of their chromosomes 1 and 16 were more frequently elongated and rearranged than those from other cell lines, which were found to be less hypomethylated. Thus, in these lymphoblastoid cell lines, alterations characterized by uncoiling and rearrangements of heterochromatic segments from chromosomes 1 and 16 seem to correlate with the hypomethylation of their repetitive DNAs. Two-color in situ hybridizations demonstrated that these elongations and rearrangements involved only classical satellite-DNA-containing heterochromatin. This specificity may be related to the excess of breakages affecting the chromosomes carrying these structures in a variety of pathological conditions.
Almeida
A
A
CNRS URA 620, Institut Curie, Paris, France.
Kokalj-Vokac
N
N
Lefrancois
D
D
Viegas-Pequignot
E
E
Jeanpierre
M
M
Dutrillaux
B
B
Malfoy
B
B
D001260:Ataxia Telangiectasia / Q000235:genetics; D015139:Blotting, Southern; D002460:Cell Line; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D002885:Chromosomes, Human, Pair 16; D004276:DNA, Satellite / Q000378:metabolism*; D005199:Fanconi Anemia / Q000235:genetics; D006570:Heterochromatin / Q000648:ultrastructure; D006801:Humans; D007621:Karyotyping; D008745:Methylation
D004276:DNA, Satellite; D006570:Heterochromatin