Polyamine depletion is associated with altered chromatin structure in HeLa cells.
HeLa cells depleted of polyamines by treatment with alpha-difluoromethylornithine (DFMO), methylglyoxal bis(guanylhydrazone) (MGBG) or a combination of the two, were examined for sensitivity to micrococcal nuclease, DNAase I and DNAase II. The degrees of chromatin accessibility to DNAase I and II appeared enhanced somewhat in all three treatment groups, and the released digestion products differed from those in non-depleted cells. DNA released from MGBG- and DFMO/MGBG-treated cells by DNAase II digestion was enriched 4-7-fold for Mg2+-soluble species relative to controls. DNA released by micrococcal nuclease digestion from all three treatment groups was characterized as consisting of higher-order nucleosomal structure than was DNA released from untreated cells. At least some of the altered chromatin properties were abolished by a brief treatment of cells with polyamines, notably spermine. These studies provide the first demonstration in vivo of altered chromatin structure in cells treated with inhibitors of polyamine biosynthesis.
Snyder
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RD
Merrell Dow Research Institute, Cincinnati, OH 45215.
D002843:Chromatin / Q000648:ultrastructure*; D003850:Deoxyribonuclease I; D015252:Deoxyribonucleases, Type II Site-Specific; D000518:Eflornithine; D006367:HeLa Cells; D006801:Humans; D008935:Mitoguazone; D011073:Polyamines / Q000037:antagonists & inhibitors*
D002843:Chromatin; D011073:Polyamines; D003850:Deoxyribonuclease I; D015252:Deoxyribonucleases, Type II Site-Specific; D008935:Mitoguazone; D000518:Eflornithine