TRRAP and GCN5 are used by c-Myc to activate RNA polymerase III transcription - PubMed (original) (raw)
TRRAP and GCN5 are used by c-Myc to activate RNA polymerase III transcription
Niall S Kenneth et al. Proc Natl Acad Sci U S A. 2007.
Abstract
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.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
Fig. 1.
TRRAP binds tRNA genes and stimulates their expression in vivo. (A) ChIP using Brf1, TRRAP, and TFIIB antibodies with HEK293 cells and primers to the indicated genes. (B) Immunoblot for TRRAP, Oct1, and actin in extracts of HeLa cells transfected with siRNAs against TRRAP or Oct1 mRNAs (lanes 1 and 2, respectively) or mock-transfected (lane 3). (C) RT-PCR of pre-tRNA and the TRRAP and ARPP P0 mRNAs in HeLa cells transfected with siRNAs against TRRAP mRNA (lanes 1 and 2), Oct1 mRNA (lanes 3 and 4), or mock-transfected (lanes 5 and 6).
Fig. 2.
TRRAP is recruited to pol III templates in response to c-Myc. (A) ChIP using RPC155, TRRAP, and TFIIB antibodies with wild-type and c-Myc null fibroblasts. (B) ChIP using c-Myc and TAFI48 antibodies with MycER-expressing fibroblasts after 0, 2, or 4 h of OHT treatment. (C) ChIP using TRRAP and TAFI48 antibodies with MycER-expressing fibroblasts after 0, 2, or 4 h of OHT treatment.
Fig. 3.
GCN5 is recruited to tRNA genes in response to c-Myc and stimulates their expression. (A) ChIP using c-Myc, GCN5, and TAFI48 antibodies with MycER-expressing fibroblasts after 0, 2, or 4 h of treatment with OHT. (B) Western blot for GCN5 and actin in extracts of HeLa cells transfected with siRNAs against GCN5 or Oct1 mRNAs (lanes 1 and 2, respectively) or mock-transfected (lane 3). (C) RT-PCR to compare levels of pre-tRNA and ARPP P0 mRNAs in HeLa cells transfected with siRNAs against GCN5 mRNA (lane 1), Oct1 mRNA (lane 2), or mock-transfected (lane 3). (D) ChIP using GCN5, TIP60, and TFIIB antibodies with matched wild-type and c-Myc knockout fibroblasts.
Fig. 4.
Induction of c-Myc stimulates H3 acetylation at pol III-transcribed genes. (A) RT-PCR of pre-tRNA and ARPP P0 mRNA in MycER-expressing fibroblasts after 0 (lanes 1 and 2) or 4 h (lanes 3–8) of OHT treatment. Where indicated, cells were pretreated for 24 h with 50 μM H3-Ac-20-Tat control peptide (lanes 5 and 6) or H3-CoA-20-Tat GCN5/PCAF inhibitor peptide (lanes 7 and 8). (B) ChIP using antibodies against TAFI48 and acetylated histones H3 and H4 with MycER-expressing fibroblasts after 0, 2, or 4 h of treatment with OHT, as indicated. Immunoprecipitated DNA was PCR-amplified by using the indicated gene primers.
Fig. 5.
Pol III and TFIIIB are recruited selectively in response to c-Myc and TSA. (A) ChIP assay using antibodies against TAFI48, RPC155, Brf1, TFIIIC220, and acetylated histones H3 and H4 with MycER-expressing fibroblasts after 0 or 4 h of treatment with OHT. Immunoprecipitated DNA was PCR-amplified by using the indicated gene primers. (B) ChIP using antibodies against Brf1 and Bdp1, TFIIIC220 and TFIIIC110, RPC155 and TAFI48, with MycER-expressing fibroblasts after 0, 2, or 4 h of treatment with OHT. Immunoprecipitated DNA was PCR-amplified by using the indicated gene primers. (C) ChIP using 5S and tRNA gene primers and antibodies against acetylated histones H3 and H4, TFIIIC (TFIIIC110), TFIIIB (Brf1), pol III (RPC155), and TFIIB with fibroblasts treated for 0, 6, 12, or 24 h with TSA.
Similar articles
- MYC interacts with the human STAGA coactivator complex via multivalent contacts with the GCN5 and TRRAP subunits.
Zhang N, Ichikawa W, Faiola F, Lo SY, Liu X, Martinez E. Zhang N, et al. Biochim Biophys Acta. 2014 May;1839(5):395-405. doi: 10.1016/j.bbagrm.2014.03.017. Epub 2014 Apr 3. Biochim Biophys Acta. 2014. PMID: 24705139 Free PMC article. - c-Myc transformation domain recruits the human STAGA complex and requires TRRAP and GCN5 acetylase activity for transcription activation.
Liu X, Tesfai J, Evrard YA, Dent SY, Martinez E. Liu X, et al. J Biol Chem. 2003 May 30;278(22):20405-12. doi: 10.1074/jbc.M211795200. Epub 2003 Mar 26. J Biol Chem. 2003. PMID: 12660246 Free PMC article. - E2F transcriptional activation requires TRRAP and GCN5 cofactors.
Lang SE, McMahon SB, Cole MD, Hearing P. Lang SE, et al. J Biol Chem. 2001 Aug 31;276(35):32627-34. doi: 10.1074/jbc.M102067200. Epub 2001 Jun 19. J Biol Chem. 2001. PMID: 11418595 - Activation by c-Myc of transcription by RNA polymerases I, II and III.
Gomez-Roman N, Felton-Edkins ZA, Kenneth NS, Goodfellow SJ, Athineos D, Zhang J, Ramsbottom BA, Innes F, Kantidakis T, Kerr ER, Brodie J, Grandori C, White RJ. Gomez-Roman N, et al. Biochem Soc Symp. 2006;(73):141-54. doi: 10.1042/bss0730141. Biochem Soc Symp. 2006. PMID: 16626295 Review. - Orchestration of chromatin-based processes: mind the TRRAP.
Murr R, Vaissière T, Sawan C, Shukla V, Herceg Z. Murr R, et al. Oncogene. 2007 Aug 13;26(37):5358-72. doi: 10.1038/sj.onc.1210605. Oncogene. 2007. PMID: 17694078 Review.
Cited by
- Gene-Specific Control of tRNA Expression by RNA Polymerase II.
Gerber A, Ito K, Chu CS, Roeder RG. Gerber A, et al. Mol Cell. 2020 May 21;78(4):765-778.e7. doi: 10.1016/j.molcel.2020.03.023. Epub 2020 Apr 15. Mol Cell. 2020. PMID: 32298650 Free PMC article. - MYC on the path to cancer.
Dang CV. Dang CV. Cell. 2012 Mar 30;149(1):22-35. doi: 10.1016/j.cell.2012.03.003. Cell. 2012. PMID: 22464321 Free PMC article. Review. - Protein acetylation and deacetylation: An important regulatory modification in gene transcription (Review).
Xia C, Tao Y, Li M, Che T, Qu J. Xia C, et al. Exp Ther Med. 2020 Oct;20(4):2923-2940. doi: 10.3892/etm.2020.9073. Epub 2020 Jul 29. Exp Ther Med. 2020. PMID: 32855658 Free PMC article. Review. - Cell growth- and differentiation-dependent regulation of RNA polymerase III transcription.
Dumay-Odelot H, Durrieu-Gaillard S, Da Silva D, Roeder RG, Teichmann M. Dumay-Odelot H, et al. Cell Cycle. 2010 Sep 15;9(18):3687-99. doi: 10.4161/cc.9.18.13203. Epub 2010 Sep 1. Cell Cycle. 2010. PMID: 20890107 Free PMC article. Review. - Myc as a Regulator of Ribosome Biogenesis and Cell Competition: A Link to Cancer.
Destefanis F, Manara V, Bellosta P. Destefanis F, et al. Int J Mol Sci. 2020 Jun 5;21(11):4037. doi: 10.3390/ijms21114037. Int J Mol Sci. 2020. PMID: 32516899 Free PMC article. Review.
References
- Grandori C, Cowley SM, James LP, Eisenman RN. Annu Rev Cell Dev Biol. 2000;16:653–699. - PubMed
- Adhikary S, Eilers M. Nat Rev Mol Cell Biol. 2005;6:635–645. - PubMed
- Oskarsson T, Trumpp A. Nat Cell Biol. 2005;7:215–217. - PubMed
- Gomez-Roman N, Grandori C, Eisenman RN, White RJ. Nature. 2003;421:290–294. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous