TRRAP and GCN5 are used by c-Myc to activate RNA polymerase III transcription

University of Glasgow, Glasgow, Scotland, United Kingdom
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 10/2007; 104(38):14917-22. DOI: 10.1073/pnas.0702909104
Source: PubMed


Activation of RNA polymerase (pol) II transcription by c-Myc generally involves recruitment of histone acetyltransferases and acetylation of histones H3 and H4. Here, we describe the mechanism used by c-Myc to activate pol III transcription of tRNA and 5S rRNA genes. Within 2 h of its induction, c-Myc appears at these genes along with the histone acetyltransferase GCN5 and the cofactor TRRAP. At the same time, occupancy of the pol III-specific factor TFIIIB increases and histone H3 becomes hyperacetylated, but increased histone H4 acetylation is not detected at these genes. The rapid acetylation of histone H3 and promoter assembly of TFIIIB, c-Myc, GCN5, and TRRAP are followed by recruitment of pol III and transcriptional induction. The selective acetylation of histone H3 distinguishes pol III activation by c-Myc from mechanisms observed in other systems.

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Available from: Natividad Gomez-Roman, Jul 02, 2014
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    • "Recently, strong evidence has implicated abnormal RNAP activity in cancer cells from breast and lung carcinomas [25] and in fibroblasts transformed by Simian virus 40 or other polyomavirus [26,27]. It is postulated that repression of tumour suppressors p53 and retinoblastoma [28] and/or activation of oncogene product c-Myc [29] may lead to enhanced RNAP activity in malignancy. However, the biological basis for an association between specific autoantibody subtypes against NRAP and malignancy in the context of SSc is unclear. "
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    Arthritis research & therapy 02/2014; 16(1):R53. DOI:10.1186/ar4486 · 3.75 Impact Factor
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    • "In support of this model, active tDNAs in vertebrates are located in nucleosome-depleted regions and flanking nucleosomes contain histone modifications associated with active promoters. In addition histone acetylases are recruited to mammalian tRNA genes suggesting that the mechanisms of insulator function in vertebrates may have similarities to those in S. cerevisiae [38] [39] [40] [41]. While numerous ETC sites have also been identified in mammalian cells [38] [40], it is currently unknown if these sites function as barrier insulators., Unlike tDNAs, ETC loci do not cluster along the DNA (JR unpublished results) and synthetic multimerized B-box sequences are not sufficient for barrier activity in murine cells [37] suggesting that these sites may have different roles but the role of these loci is unclear at this time. "
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    ABSTRACT: tRNA genes (tDNAs) have been known to have barrier insulator function in budding yeast, Saccharomyces cerevisiae, for over a decade. tDNAs also play a role in genome organization by clustering at sites in the nucleus and both of these functions are dependent on the transcription factor TFIIIC. More recently TFIIIC bound sites devoid of pol III, termed Extra-TFIIIC sites (ETC) have been identified in budding yeast and these sites also function as insulators and affect genome organization. Subsequent studies in Schizosaccharomyces pombe showed that TFIIIC bound sites were insulators and also functioned as Chromosome Organization Clamps (COC); tethering the sites to the nuclear periphery. Very recently studies have moved to mammalian systems where pol III genes and their associated factors have been investigated in both mouse and human cells. Short interspersed nuclear elements (SINEs) that bind TFIIIC, function as insulator elements and tDNAs can also function as both enhancer — blocking and barrier insulators in these organisms. It was also recently shown that tDNAs cluster with other tDNAs and with ETCs but not with pol II transcribed genes. Intriguingly, TFIIIC is often found near pol II transcription start sites and it remains unclear what the consequences of TFIIIC based genomic organization are and what influence pol III factors have on pol II transcribed genes and vice versa. In this review we provide a comprehensive overview of the known data on pol III factors in insulation and genome organization and identify the many open questions that require further investigation. This article is part of a Special Issue entitled: Transcription by Odd Pols.
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    • "Intriguingly, these MDSR genes are largely involved in nucleotide metabolism, ribosome biogenesis, RNA processing and DNA replication. In this regard, Myc also regulates RNA polymerases I and III mediated transcription in addition to its role in regulating RNA Pol II genes (Felton-Edkins et al., 2003; Gomez-Roman et al., 2003; Grandori et al., 2005; Kenneth et al., 2007). Thus, the protein biosynthetic machinery is inherent linked to Myc transcriptional activity and the balance between rRNA synthesis, ribosomal protein production, and the availability of adequate bioenergetics is essential for normal cell growth. "
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