EPIGENETIC CONTROL OF MAMMALIAN CENTROMERE PROTEIN-BINDING - DOES DNAMETHYLATION HAVE A ROLE

Chromosome 1 of the inbred mouse strain DBA/2 has a polymorphism assoc iated with the minor satellite DNA at its centromere. The more termina l block of satellite DNA sequences on this chromosome acts as the cent romere as shown by the binding of CREST ACA serum, anti-CENP-B and ant i-CENP-E polyclonal sera, Demethylation of the minor satellite DNA seq uences accomplished by growing cells in the presence of the drug 5-aza -2'-deoxycytidine results in a redistribution of the CENP-B protein, T his protein now binds to an enlarged area on the more terminal block a nd in addition it now binds to the more internal block of minor satell ite DNA sequences on chromosome 1, The binding of the CENP-E protein d oes not appear to be affected by demethylation of the minor satellite sequences. We present a model to explain these observations, This mode l may also indicate the mechanism by which the CENP-B protein recognis es specific sites within the arrays of minor satellite DNA on mouse ch romosomes.