Disease relevance of GTF2H1

• Genetic studies indicate that this transcription-coupled repair is dependent on the Cockayne syndrome group A and B proteins, as well as TFIIH subunits [1].
• Evidence presented here indicates that this complex can interact with a factor containing the TFIIH core subunits p62 and xeroderma pigmentosum subunit B/excision repair cross-complementing 3 [1].
• Because transcriptionally generated torsion melts FUSE in vitro even in linear DNA, and FBP/FBP Interacting Repressor (FIR) regulates transcription through TFIIH, these components have been speculated to be the mechanosensor (FUSE) and effectors (FBP/FIR) of a real-time mechanism controlling c-myc transcription [2].
• We conclude that the recruitment and activation of TFIIH represents a rate-limiting step for the emergence of HIV from latency [3].

High impact information on GTF2H1

• By contrast, TFIIE, TFIIH, and ATP hydrolysis were additionally required during promoter clearance from linear templates, while negative supercoiling obviated the need for these auxiliary factors [4].
• FBP bound to FUSE acts through TFIIH at the promoter [5].
• Sequence similarity suggests that BTF2 may be the human counterpart of RNA polymerase II initiation factor b from yeast [6].
• The interaction between the amino-terminal transactivation domain (TAD) of p53 and TFIIH is directly correlated with the ability of p53 to activate both transcription initiation and elongation [7].
• To study TFIIH in vivo, we generated cell lines expressing functional GFP-tagged TFIIH [8].

Biological context of GTF2H1

• Residues phosphorylated by TFIIH are required for E2F-1 degradation during S-phase [9].
• Point mutations in VP16 that reduce its transactivation activity in both yeast and mammalian cells weaken its binding to both yeast and human TFIIH [10].
• Here we demonstrate for the first time that TFIIH-mediated phosphorylation of RNA polymerase II (Pol II) is essential for the transition to elongation [11].
• Transcription factor IIH (TFIIH) is involved both in transcription initiation by RNA polymerase II and in nucleotide excision-repair [1].
• Using chromatin immunoprecipitation assays, we showed that TFIIH subunits were corecruited on or near an endogenous thyroid hormone response element upon T3 addition [12].

Anatomical context of GTF2H1

• To investigate the potential role of the general transcription factor, TFIIH, in T3-mediated transcriptional activation, we examined thyroid hormone receptor (TR) interaction with individual TFIIH subunits in a yeast-two hybrid system [12].
• In addition to these small domains, TFIIH was found concentrated in coiled bodies and Oct1 in a single large domain of about 1.5 microm in 30% of the cells in an asynchronous HeLa cell culture [13].
• Our data are consistent with the possibility that in living Chironomus salivary gland cells, DRB interferes with the recruitment of TFIIF, but not of TFIIH, to the promoter by interference with the activity of the CK2alpha subunit enzyme and phosphorylation of RAP74 and thereby DRB blocks transcription initiation [14].
• To investigate the role of TFIIH during HIV reactivation in vivo, we developed a population of Jurkat cells containing integrated, but transcriptionally silent, HIV proviruses [3].

Associations of GTF2H1 with chemical compounds

• NMR structure of the amino-terminal domain from the Tfb1 subunit of TFIIH and characterization of its phosphoinositide and VP16 binding sites [15].
• In contrast, the binding of hypophosporylated pol II and TFIIH to the active gene loci is not abolished by the DRB regimen [14].
• Upon stimulation of the cells by TNF-alpha, NF-kappaB and TFIIH are rapidly recruited to the promoter together with additional Mediator and RNAP II, but CDK8 is lost [3].

Physical interactions of GTF2H1

• We showed that hnRNP U can bind TFIIH in vivo under certain conditions and inhibit TFIIH-mediated CTD phosphorylation in vitro [16].
• Only 4 of 10 possible interactions were found above the detection limit: TFIIB, -E, and -F binding to RNA polymerase II and TFIIE binding to TFIIH [17].

Enzymatic interactions of GTF2H1

• The preferred substrate for SCP1 is RNAP II phosphorylated by TFIIH [18].

Co-localisations of GTF2H1

• Furthermore, FBP co-localized with transcription sites and with the general transcription factor TFIIH, but not with the splicing factor SC-35 [19].

Regulatory relationships of GTF2H1

• The abilities of hnRNP U to inhibit TFIIH-mediated CTD phosphorylation and its Pol II association are necessary for hnRNP U to mediate the repression of Pol II elongation [16].
• hnRNP U inhibits carboxy-terminal domain phosphorylation by TFIIH and represses RNA polymerase II elongation [16].

Other interactions of GTF2H1

• We report a dramatic inhibition of XPA and p62-TFIIH association with UVC photoproducts on linear DNA [20].
• We show that pX interacts with general transcription factors TFIIB and TFIIH, as well as with the potent activation domain of VP16 [21].
• We find that the middle domain of hnRNP U is sufficient to mediate its Pol II association and its inhibition of TFIIH-mediated phosphorylation and Pol II elongation [16].
• In contrast, a significant but incomplete overlap was observed between the spatial distributions of transcription sites and BRG1 and TFIIH [13].

Analytical, diagnostic and therapeutic context of GTF2H1

• The binding of two NER proteins, XPA and p62-TFIIH, indispensable for the incision step of the reaction, was quantified either directly in an ELISA-like reaction in the wells with specific antibodies or in Western blotting experiments on the DNA-bound fraction [20].
• The results obtained from our immunoprecipitation experiment further demonstrated that the ATM protein interacted with the TFIIH basal transcription factor and the XPG protein of the NER pathway [22].

References