ABNORMAL METHYLATION PATTERN IN CONSTITUTIVE AND FACULTATIVE (X-INACTIVE CHROMOSOME) HETEROCHROMATIN OF ICF PATIENTS

We have investigated the distribution of DNA methylation in chromosome s and nuclei of normal individuals and lCF (Immunodeficiency, Centrome ric instability and Facial abnormalities) syndrome patients, using 5-m ethylcytosine monoclonal antibody, In this syndrome, DNA digestion wit h methyl-sensitive enzymes has previously shown a specific hypomethyla tion of classical satellites located in constitutive heterochromatin. The chromosome methylation pattern confirms this hypomethylation showi ng in addition a clear undermethylation of facultative heterochromatin (X inactive chromosome), Antibodies give, in normal and ICF chromosom es, a non-uniform labeling of euchromatin, generating a weak R-like ba nding pattern on chromosomes, This pattern reflects an unequal distrib ution of DNA methylation over the genome disclosing another aspect of chromosome organization, The breakpoints of chromosome rearrangements and the heterochromatin stretchings observed in ICF patients were anal yzed by means of in situ hybridization. These chromosome modifications involve hypomethylated classical DNA satellite sequences, The underly ing hypomethylation, associated with an abnormal chromatin organizatio n, may predispose to chromosome instability.