Disease relevance of GTF3C1

• Transcription factor IIIC (TFIIIC) is required for the assembly of a preinitiation complex on 5S RNA, tRNA, and adenovirus VA RNA genes and contains two separable components, TFIIIC1 and TFIIIC2 [1].
• The human immunodeficiency virus tat protein increases the transcription of human Alu repeated sequences by increasing the activity of the cellular transcription factor TFIIIC [2].
• During poliovirus infection, TFIIIC is cleaved and inactivated by the poliovirus-encoded 3C protease (3Cpro) [3].
• Human transcription factor IIIC (hTFIIIC) is a multisubunit complex that mediates transcription of class III genes through direct recognition of promoters (for tRNA and virus-associated RNA genes) or promoter-TFIIIA complexes (for the 5S RNA gene) and subsequent recruitment of TFIIIB and RNA polymerase III [4].
• Incubation of purified 3Cpro, expressed in Escherichia coli, with transcriptionally active TFIIIC (complex I) in vitro resulted in generation of the transcriptionally inactive complex III form of TFIIIC [5].

High impact information on GTF3C1

• TFIIIB can associate with the evolutionarily conserved C-terminal domain of TBP in the absence of DNA or TFIIIC, suggesting that TFIIIB exists in solution as a complex with TBP [6].
• The in vitro interconversion of the two forms of TFIIIC by phosphatase treatment suggests that transcriptional activation of RNA polymerase III genes can be mediated by phosphorylation of TFIIIC [7].
• Here, it is shown that all components required for transcription of the VA1 and tRNA genes, including TFIIIB, TFIIIC, and RNA Pol III, can be coimmunopurified from a HeLa cell line that constantly expresses a FLAG epitope-tagged subunit of human RNA Pol III [8].
• Human TFIIIC relieves chromatin-mediated repression of RNA polymerase III transcription and contains an intrinsic histone acetyltransferase activity [9].
• The possibility of a direct link between TFIIIC-dependent chromatin transcription and acetyltransferase activities is suggested by the partial loss of these activities, but not DNA transcription activity, following pretreatment of TFIIIC with p-hydroxymercuribenzoic acid [9].

Biological context of GTF3C1

• Previous studies have shown that increases in RNA polymerase III activity during infection of cells by adenovirus (with concomitant E1A expression) or during cell growth at high serum concentration results from an increased activity in the TFIIIC fraction [10].
• TFIIIC then directs the binding of TFIIIB to DNA upstream of the transcription start site [3].
• We show that the induced TFIIIC110 enters the nucleus, binds other TFIIIC subunits and is recruited to tRNA and 5S rRNA genes in vivo [11].
• These results indicate that the nascent transcript contacts the two largest subunits of RNA polymerase III until the transcription complex reaches the TFIIIC binding site, at which point the nascent transcript contacts TFIIIC [12].
• Chemical nuclease footprinting of TFIIIC- and TFIIIB-TFIIIC-DNA complexes reveals that Nhp6a markedly alters the TFIIIC footprint over box A and reduces the size of the TFIIIB footprint on upstream DNA sequence [13].

Anatomical context of GTF3C1

• We showed previously that HeLa cell nuclear extracts contain two forms of transcription factor IIIC (TFIIIC) that formed chromatographically distinct TFIIIC-promoter complexes (Hoeffler, W. K., Kovelman, R., and Roeder, R. G. (1988) Cell 53, 907-920) [14].

Associations of GTF3C1 with chemical compounds

• The formation of the corresponding 0.015% Sarkosyl-resistant complex required the presence of TFIIIC, TFIIIB, and RNA polymerase III but not nucleoside triphosphates [15].
• TPCK and N-ethylmaleimide inactivated TFIIIC solely through thiol group modification, since prior modification with the reversible thiol reagent 2,2'-dithiopyridine prevented permanent inactivation [16].
• The involvement of reduced thiol groups in the specific binding of TFIIIC to the VAI gene was further indicated by an increase in TFIIIC binding activity upon addition of dithiothreitol [16].

Physical interactions of GTF3C1

• These results show that hTFIIIC binds to its promoter sequences in a metal coordinated fashion which differs from that observed for the binding of hTFIIIA to the 5S gene [17].
• In this fraction a polypeptide with a molecular mass of approximately 110 kDa could be identified as a specific DNA-binding component of hTFIIIC [18].

Regulatory relationships of GTF3C1

• In mammalian cells, regulation of TFIIIC activity controls overall polymerase III transcription in response to growth factors and viral infection [19].

Other interactions of GTF3C1

• In contrast, restoration of 5S RNA gene transcription requires readdition of both TFIIIC and TFIIIA, indicating a promoter-independent interaction between these factors [1].
• Furthermore, immunodepletion assays indicate that TFIIIC alpha is absolutely required for RNA polymerase III transcription of 5S RNA, tRNA, and VAI RNA genes but not for the 7SK RNA and U6 small nuclear RNA genes [1].
• In addition, NF1 acts in conjunction with TFIIIC to promote accurate termination by RNA polymerase III on a C-tailed VA1 template [20].
• Autoinhibition of TFIIIB70 binding by the tetratricopeptide repeat-containing subunit of TFIIIC [21].
• Transcription factor IIIC from human cells (hTFIIIC) contains a 55 kDa polypeptide which specifically binds to the promoter of the VAI and 5S gene [17].

Analytical, diagnostic and therapeutic context of GTF3C1

• Using gel retardation assays, we have shown previously that inhibition of pol III transcription by poliovirus is correlated with disappearance of a transcriptionally active form of TFIIIC (complex I) concomitant with the appearance of a faster mobility, transcriptionally inactive form of TFIIIC (complex III) [5].
• Template commitment titrations further suggest that the increased TFIIIC activity was due to an increase in the concentration of active TFIIIC [22].
• This activity copurified through all chromatographic procedures, including B-block oligodeoxynucleotide affinity chromatography, with the two forms of TFIIIC detected by gel mobility shift assays with the VA gene (Hoeffler, W.K., Kovelman, R., and Roeder, R.G. (1988) Cell 53, 907-920) [16].
• The near identity of the TFIIIC molecular weight determined by gel filtration on SOTA Phase GF 200 (Mr = 140,000) suggests that TFIIIC in solution (in the presence of 0.3 M NaCl at pH 7.0) consists of a single polypeptide which is fairly globular in nature [16].

References