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 biogenesis 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 molecular mechanisms responsible for this inhibitory process. Our analysis indicates that the activity of the TATA binding protein (TBP)/TBP-associated factor (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 activity is not a consequence of a decrease in SL1, because there is no detectable difference in the abundance of TBP or TAFs before and after U937 cell differentiation. In conclusion, our results indicate that the selectivity factor SL1 is an important target for the regulation of pol I transcription during cell differentiation.
Comai
L
L
Department of Molecular Microbiology and Immunology and K. Norris Jr. Comprehensive Cancer Center, University of Southern California, School of Medicine, Los Angeles 90033, USA.
Song
Y
Y
Tan
C
C
Bui
T
T
D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D035463:Pol1 Transcription Initiation Complex Proteins; D012318:RNA Polymerase I / Q000037:antagonists & inhibitors*; D035181:TATA-Box Binding Protein; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D020298:U937 Cells / Q000201:enzymology
D004268:DNA-Binding Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; C063660:transcription initiation factor TIF-IB; D012318:RNA Polymerase I; D013755:Tetradecanoylphorbol Acetate