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p53 represses RNA polymerase III transcription by targeting TBP and inhibiting promoter occupancy by TFIIIB
Author(s) -
Crighton Diane,
Woiwode Annette,
Zhang Cheng,
Mandavia Nihar,
Morton Jennifer P.,
Warnock Lorna J.,
Milner Jo,
White Robert J.,
Johnson Deborah L.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg265
Subject(s) - rna polymerase iii , biology , tata binding protein , rna polymerase ii , microbiology and biotechnology , transcription (linguistics) , transcription factor ii d , chromatin immunoprecipitation , transcription factor , rna , rna polymerase , promoter , genetics , gene , gene expression , dna binding protein , linguistics , philosophy
The tumor suppressor p53 is a transcription factor that controls cellular growth and proliferation. p53 targets include RNA polymerase (pol) III‐dependent genes encoding untranslated RNAs such as tRNA and 5S rRNA. These genes are repressed through interaction of p53 with TFIIIB, a TATA‐binding protein (TBP)‐containing factor. Although many studies have shown that p53 binds to TBP, the significance of this interaction has remained elusive. Here we demonstrate that the TBP–p53 interaction is of functional importance for regulating RNA pol III‐transcribed genes. Unlike RNA pol II‐dependent promoter repression, overexpressing TBP can reverse inhibition of tRNA gene transcription by p53. p53 does not disrupt the direct interaction between the TFIIIB subunits TBP and Brf1, but prevents the association of Brf1 complexes with TFIIIC2 and RNA pol III. Using chromatin immunoprecipitation assays, we found that TFIIIB occupancy on tRNA genes markedly decreases following p53 induction, whereas binding of TFIIIC2 to these genes is unaffected. Together our results support the idea that p53 represses RNA pol III transcription through direct interactions with TBP, preventing promoter occupancy by TFIIIB.