ANALYSIS OF CHROMATIN STRUCTURE OF RAT ALPHA(1)-ACID GLYCOPROTEIN GENE - CHANGES IN DNASE-I HYPERSENSITIVE SITES AFTER THYROID-HORMONE, GLUCOCORTICOID HORMONE AND TURPENTINE-OIL TREATMENT

Transcription of the rat alpha(1)-acid glycoprotein (AGP) gene is acti vated by glucocorticoid, thyroid hormone (T-3) and cytokines, Followin g these treatments, the chromatin structure of this gene was analyzed by means of digestion with DNase I or micrococcal nuclease, Four DNase I hypersensitive sites were observed in the 5'-upstream region of the rat AGP gene of liver cells, They were designated HS1, HS2, HS3 and H S4 (3'-->5'). After T-3 treatment the sensitivity of HS1 and HS2 incre ased and after dexamethasone (Dex) treatment that of all four sites di d so. Three new sites appeared after turpentine oil treatment, while t he sensitivities of HS3 and HS4 increased, We conclude that transcript ional activation of the gene by T-3 and Dex have very similar mechanis ms, but that at the inflammation stage they become slightly different, The increase in sensitivity at HS1 and HS2 after T-3 treatment in viv o was successfully reproduced in a cell-free system by in vitro treatm ent with T-3. HS1, HS2 and HS3 were also sensitive for micrococcal nuc lease.