Inhibition of RNA polymerase I transcription in differentiated myeloid leukemia cells by inactivation of selectivity factor 1

Transcription by RNA polymerase I (pol I) regulates the rate of ribosome bi ogenesis and the biosynthetic potential of the cell; therefore, it plays an important role in the control of cell growth. Differentiation of the human promyelocytic leukemic cell line U937 is accompanied by drastic decreases in pol I transcriptional activity. We have used cell-free extracts prepared from undifferentiated and differentiated U937 cells to investigate the mol ecular mechanisms responsible for this inhibitory process. Our analysis ind icates that the activity of the TATA binding protein (TBP)/TBP-associated f actor (TAF) complex selectivity factor 1 (SL1), one of the factors required for accurate and promoter-specific transcription by RNA pol I, is severely repressed in differentiated U937 cells. Moreover, the reduction in SL1 act ivity is not a consequence of a decrease in SL1, because there is no detect able difference in the abundance of TBP or TAFs before and after U937 cell differentiation. In conclusion, our results indicate that the selectivity f actor SL1 is an important target for the regulation of pol I transcription during cell differentiation.