ALPHA-SATELLITE DNA METHYLATION IN NORMAL INDIVIDUALS AND IN ICF PATIENTS - HETEROGENEOUS METHYLATION OF CONSTITUTIVE HETEROCHROMATIN IN ADULT AND FETAL TISSUES

The methylation profile of ten alpha-satellites was investigated in no rmal individuals and in ICF (Immunodeficiency, Centromeric instability , Facial abnormalities) patients. Two out of three ICF patients showed modified methylation of these sequences, reproducing a placental prof ile. CENP-B boxes, the binding sites of centromeric protein B, were al ways skewed toward nonmethylation. Unexpected results were observed in normal individuals: in somatic adult tissues the methylation pattern of alpha-satellite DNA varied between chromosomes, and in fetal tissue s these satellites were homogeneously undermethylated. Detailed methyl ation analysis of CENP-B boxes revealed that unmethylated alpha-satell ite units coexist with thoroughly methylated regions. These observatio ns showed that the two major components of constitutive heterochromati n are differently methylated in normal somatic and fetal tissues, sinc e classical satellites are consistently methylated. The definite chang es in the methylation profile of heterochromatin in somatic chromosome s and the asynchronous timing of methylation of classical and alpha-sa tellites during development may reflect specific roles of highly repea ted sequences in genomic organization.