Structurally altered and transcriptionally activated rat prostate chromatin induced by androgens

Abstract

The effect of androgens on the structure and transcriptional function of rat prostate chromatin was investigated by the following studies: template activity in transcription, distribution of euchromatin and heterochromatin, titration with polylysine, thermal denaturation and circular dichroism spectra. Following a single intraperitoneal injection of testosterone to rats, the template activity of prostate chromatin, assayed in rat liver RNA polymerase (RNA nucleotidyltransferase, EC 2.7.7.6) II reaction, increased by 68% 2 h (CT 2) after hormone administration; while the template activities of prostate chromatins from rats receiving testosterone for 4 (CT 4), 6 (CT 6) and 12 h (CT 12) were slightly lower than that of the castrated control (C). Similar patterns were also observed in polylysine binding by, and distribution of euchromatin and heterochromatin in, the various prostate chromatins. The template activity of prostate chromatin in rat liver RNA polymerase II reaction was contributed exclusively by its euchromatin fraction. Furthermore, CT 2 euchromatin was also found to have the highest template activity than CT 4, CT 6, CT 12 and C euchromatins. Derivative melting profiles of the various chromatins all showed increased melting of DNA regions bound by nonhistone proteins with concomitant decreases in histone-bound regions of DNA. Circular dichroism spectra of these chromatins showed conformational changes in proteins, as indicated by a reduction in amplitude at 210–220 nm, for CT 2 chromatin, and increases for CT 4, CT 6 and CT 12 chromatins when compared with the control. These results indicate that androgen action in gene activation is related to structural alterations of prostate chromatin induced by androgens.