Correlation of rat liver chromatin-bound free and esterified cholesterol with the circadian rhythm of cholesterol biosynthesis in the rat.
Cholesterol has been shown to be present in rat liver chromatin isolated by methods designed to avoid contamination by membrane fragments. Evidence that the cholesterol was actually a component of chromatin includes (a) the constancy of the amount (1.30 +/- 0.14 mug per mg DNA), (b) the striking difference in the ratio of free (i.e. unesterified) to esterified cholesterol between that in chromatin and that in membrane, and (c) the rapid and marked changes which occurred in this ratio during the circadian cycle in chromatin but not in membranes. Although the total amount of chromatin-bound cholesterol did not change throughout the circadian cycle, the concentration of free cholesterol increased sharply a short time before the peak of cholesterol synthetic activity was reached at about midnight; it reached a basal level about 6 h later at approximately the same time the rate of synthesis returned to its basal level. When labelled cholesterol was administered by stomach tube, it was detectable within 2 h in whole nuclei and in chromatin, indicating that chromatin-bound cholesterol is rapidly exchangeable with that in liver cytoplasm and in blood plasma. Removal of basic proteins from chromatin did not result in the loss of any cholesterol, but removal of most of the acidic as well as the basic proteins resulted in loss of most of the chromatin-bound cholesterol. These results indicate that cholesterol is bound either to the acidic proteins or to both the acidic proteins and DNA. The data are compatible with the hypothesis that cholesterol biosynthesis controlled at the nuclear level and suggest that the relative amounts of free and esterified cholesterol associated with chromatin may play a role.
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D002940:Circadian Rhythm; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000032:analysis; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011506:Proteins / Q000032:analysis; D051381:Rats
D002788:Cholesterol Esters; D002843:Chromatin; D010743:Phospholipids; D011506:Proteins; D004247:DNA; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases