© 1994 Oxford University Press
RESEARCH-ARTICLE |
Abnormal methylation pattern in constitutive and facultative (X inactive chromosome) heterochromatin of ICF patients
U383 INSERM, Hopital Necker-Enfants Malades 149, rue de Sè vres, 75743 Paris Cedex 15 1U129 INSERM and Service de Biochimie Génétique, ICGM, CHU Cochin 24 rue du Faubourg Saint-Jacques, 75014 Paris 2Centre Hospitaller Ré gional et Universitaire de Poitiers, Hopital Jean-Bernard BP 577–86021 Poitiers 3U132 INSERM, Hopital Necker-Enfants Malades, 149, rue de Sè vres 75743 Paris Cedex 15 4lnstitut Pasteur de Lyon, CNRS URA 1459, Département de Virologie, av. Tony Garnier 69365 Lyon Cedex 07, France
*To whom correspondence should be addressed
Received July 1, 1994; Accepted September 23, 1994
We have investigated the distribution of DNA methylatlon In chromosomes and nuclei of normal individuals and ICF (Immunodeficiency, Centromeric Instability and Facial abnormalities) syndrome patients, using 5-methyl-cytosine monoclonal antibody. In this syndrome, DNA digestion with methyl-sensitive enzymes has previously shown a specific hypomethylation of classical satellites located In constitutive heterochromatin. The chromosome methylatlon pattern confirms this hypomethylation showing In addition a clear undermethylatlon of facultative heterochromatin (X Inactive chromosome). Antibodies give, In normal and ICF chromosomes, a non-uniform labeling of euchromatin, generating a weak R-IIke banding pattern on chromosomes. This pattern reflects an unequal distribution 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 analyzed by means of In situ hybridization. These chromosome modifications Involve hypomethylated classical DNA satellite sequences. The underlying hypomethylation, associated with an abnormal chromatln organization, may predispose to chromosome Instability.
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