Sequential activation of splenic nuclear RNA polymerases by erythropoietin

The spleen of the ex-hypoxic polycythemic mouse was employed to study the effect of erythropoietin on nuclear RNA polymerase activity. On the basis of ionic strength requirements and sensitivity to the fungal toxin alpha-amanitin, two major forms (I and II) of nuclear RNA polymerase were identified. Within 0.5 h after administration of erythropoietin, at a time when no morphologically identifiable erythroblasts were present in the spleen, there was an increase in the activity of polymerase II. By 2 h, polymerase II activity had declined to control levels. At 3 h, polymerase I activity began to increase, rising to a peak, 88% above control levels, by 12 h. During this period, early erythroblasts began to appear in the spleen. At 12 h, a second increase of similar magnitude occurred in polymerase II activity. Polymerase I activity fell to control levels by 18 h while polymerase II declined more slowly. These data indicate that stimulation of transcription is an early effect of erythropoietin. Multiple forms of RNA polymerase are involved and activation of these is sequential. Nuclear RNA polymerase activity is maximal during the period of early erythroblast proliferation and declines as these cells mature.