Mammalian Maf1 is a negative regulator of transcription by all three nuclear RNA polymerases.
Most eukaryotic transcriptional regulators act in an RNA polymerase (Pol)-selective manner. Here we show that the human Maf1 protein negatively regulates transcription by all three nuclear Pols. Changes in Maf1 expression affect Pol I- and Pol III-dependent transcription in human glioblastoma lines. These effects are mediated, in part, through the ability of Maf1 to repress transcription of the TATA binding protein, TBP. Maf1 targets an Elk-1-binding site in the TBP promoter, and its occupancy of this region is reciprocal with that of Elk-1. Similarly, Maf1 occupancy of Pol III genes is inversely correlated with that of the initiation factor TFIIIB and Pol III. The phenotypic consequences of reducing Maf1 expression include changes in cell morphology and the accumulation of actin stress fibers, whereas Maf1 overexpression suppresses anchorage-independent growth. Together with the ability of Maf1 to reduce biosynthetic capacity, these findings support the idea that Maf1 regulates the transformation state of cells.
Johnson
Sandra S
SS
Department of Biochemistry and Molecular Biology, Keck School of Medicine and the Norris Comprehensive Cancer Center, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.
Zhang
Cheng
C
Fromm
Jody
J
Willis
Ian M
IM
Johnson
Deborah L
DL
D001665:Binding Sites; D048708:Cell Growth Processes; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D012318:RNA Polymerase I / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D012320:RNA Polymerase III / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000378:metabolism; D035181:TATA-Box Binding Protein / Q000235:genetics / Q000378:metabolism*; D035361:Transcription Factor TFIIIB / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured
C427472:BDP1 protein, human; C441028:BRF1 protein, human; C520535:MAF1 protein, human; D012097:Repressor Proteins; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D035361:Transcription Factor TFIIIB; D012319:RNA Polymerase II; D012321:DNA-Directed RNA Polymerases; D012318:RNA Polymerase I; D012320:RNA Polymerase III