Chemical inducers of differentiation cause conformational changes in the chromatin and deoxyribonucleic acid of murine erythroleukemia cells.

The chemical inducers of murine erythroleukemia cell differentiation, dimethyl sulfoxide, sodium butyrate, and ethionine, elicited conformational changes in the DNA and chromatin of treated cells. The chromatin from dimethyl sulfoxide treated and butyrate-treated cells exhibited circular dichroic spectra different from that of the noninduced control. The molar ellipticity [theta]282.5 in isotonic saline decreased from 4900 deg X cm2 X dmol-1 for control chromatin to 3800 and 3600 deg X cm2 X dmol-1 for dimethyl sulfoxide treated and butyrate-treated chromatin, respectively, while that from ethionine-treated chromatin remained virtually unchanged (5400 deg X cm2 X dmol-1). Increasing the ionic strength to 2.5 or 5 M with NaCl resulted in a substantial, uniform, decrease in molar ellipticity. Thermal denaturation profiles of high molecular weight DNA prepared from each of the inducer-treated cells showed a pronounced hyperchromic shift but no change in Tm when compared to control DNA. Circular dichroic spectra of the DNA indicated a decrease in ellipticity [theta]277 from 9600 deg X cm2 X dmol-1 to 8900, 8300, and 8800 deg X cm2 X dmol-1 for ethionine, dimethyl sulfoxide, and butyrate treated cells, respectively. Treatment of the DNA with 3 M NaCl canceled the UV and CD differences. These measurements indicate an increased stacking of bases or an increased compactness of the DNA from induced cells. Concomitant with specific modifications such as hypomethylation of DNA, the data can be interpreted in terms of conformational changes in chromatin resulting from core histone acetylation.