The Wilms' tumor suppressor gene (wt1) product represses different functional classes of transcriptional activation domains.
We have studied the ability of the wt1 tumor suppressor gene product to repress different classes of activation domains previously shown to stimulate the initiation and elongation steps of RNA polymerase II transcription in vivo. Repression assays revealed that WT1 represses all three classes of activation domains: Sp1 and CTF, which stimulate initiation (type I), human immunodeficiency virus type I Tat fused to a DNA-binding domain, which stimulates predominantly elongation (type IIA), and VP16, p53 and E2F1, which stimulate both initiation and elongation (type IIB). WT1 is capable of exerting its repression effect over a significant distance when positioned approximately 1700 bp from the core promoter. Deletion analysis of WT1 indicates that the responsible domain resides within the first 180 N-terminal amino acids of the protein. Nuclear run-ons analyzing the effects of WT1 on initiation of transcription demonstrate inhibition of this process. Our observations imply that WT1 can repress activators that stimulate initiation and/or elongation.
Lee
T H
TH
Department of Biochemistry, McGill Cancer Center, McGill University, Montreal, Quebec H3 1 Y6, Canada.
Moffett
P
P
Pelletier
J
J
D000818:Animals; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D017405:Herpes Simplex Virus Protein Vmw65 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D051839:NFI Transcription Factors; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D025721:WT1 Proteins; D009396:Wilms Tumor / Q000235:genetics
D022762:CCAAT-Enhancer-Binding Proteins; C077305:CTF-1 transcription factor; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015696:Gene Products, tat; D017405:Herpes Simplex Virus Protein Vmw65; D051839:NFI Transcription Factors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D056465:Retinoblastoma-Binding Protein 1; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins