Torsional stress promotes the DNAase I sensitivity of active genes

Active genes are known to have an altered chromatin structure that is preferentially sensitive to digestion with DNAase I. We find that when chicken red blood cells are incubated in media containing the topoisomerase II inhibitor novobiocin, the preferential DNAase I sensitivity of the active beta-globin genes is reversed in vivo with as little as 20 min of drug treatment. Control experiments suggest that inhibition of a topoisomerase II is responsible for this alteration in active gene conformation. Reversal of DNAase I sensitivity can also be induced in vitro by partial cleavage of the nuclear DNA with staphylococcal nuclease. We propose that the altered structure around active genes is maintained by continuous DNA supercoiling and that in the absence of this superhelical tension active chromatin reverts to a less DNAase I-sensitive ground state.