Changes in transcriptional activity during myocardial hypertrophy.

We have demonstrated alterations in the composition of certain groups of nuclear no-histone proteins which could account for the changes in template activity. Further identification of the individual proteins essential for this regulation will aid us in our understanding of the mechanism of myocardial cell growth during hypertrophy. We also have demonstrated the existence of several different RNA polymerase enzymes and have characterized them. The question of de novo synthesis or activation of preexisting enzyme remains unanswered. The delay in changes in activity which we found is also of great interest and may provide information as to the mechanism of increased RNA polymerase activity. The regulation of transcription can occur by changes either in the activity of the chromatin template or in the activities of the various RNA polymerase. Our studies thus far strongly suggest that during the development of hypertrophy both regulatory mechanisms are operative. Furthermore, this appears to be a bimodal function; initially there are changes only in the template and only later do changes in enzyme activity occur. To our knowledge this is the first demonstration of this form of regulation of RNA synthesis in myocardial tissue.