HISTONE H4 ACETYLATION ANALYSES IN PATIENTS WITH POLYSOMY X - IMPLICATIONS FOR THE MECHANISM OF X-INACTIVATION

In humans, it is thought that the X-inactivation phenomenon occurs no matter how many X chromosomes are present, and that only one of them r emains active. Nevertheless, individuals who have an abnormal number o f X chromosomes show a wide spectrum of abnormalities, which increase with the number of X chromosomes present in a given individual. It has been shown that the inactive X chromosome in female mammals is distin guished by a lack of histone H4 acetylation, and that this could be us ed as an accessible marker for distinguishing between Xi and Xa in spr eads of metaphase chromosomes. We studied three X-polysomic patients f or the presence of active chromatin by analysis of histone H4 acetylat ion on unfixed metaphase spreads. Using antisera to H4 acetylated at l ysines 16, 8 and 5, respectively, we observed frequencies different fr om those expected from cells with only one underacetylated X chromosom e. In particular, when antiserum to H4 acetylated at lysine 16 was use d about 90% of the cells showed acetylation of all X chromosomes. This suggests a possible disturbance in the deacetylation process, probabl y due to the presence of multiple Xs.