HYPOMETHYLATION OF CLASSICAL SATELLITE DNA AND CHROMOSOME INSTABILITYIN LYMPHOBLASTOID CELL-LINES

To determine possible relationships between DNA hypomethylation and ch romosome instability, human lymphoblastoid cell lines from different g enetic constitutions were studied with regard to 1) uncoiling and rear rangements, which preferentially affect the heterochromatic segments o f chromosomes 1 and 16; 2) the methylation status of the tandemly repe titive sequences (classical satellite and alphoid DNAs) from chromosom es 1 and 16, and of the L1Hs interspersed repetitive sequences. The me thylation status largely varied from cell line to cell line, but for a given cell line, the degree of methylation was similar for all the re petitive DNAs studied. Two cell lines, one obtained from a Fanconi ane mia patient and the other from an ataxia telangiectasia patient were f ound to be heavily hypomethylated. The heterochromatic segments of the ir chromosomes 1 and 16 were more frequently elongated and rearranged than those from other cell lines, which were found to be less hypometh ylated. Thus, in these lymphoblastoid cell lines, alterations characte rized by uncoiling and rearrangements of heterochromatic segments from chromosomes 1 and 16 seem to correlate with the hypomethylation of th eir repetitive DNAs. Two-color in situ hybridizations demonstrated tha t these elongations and rearrangements involved only classical satelli te-DNA-containing heterochromatin. This specificity may be related to the excess of breakages affecting the chromosomes carrying these struc tures in a variety of pathological conditions.