Genomes and Genes
transcriptional elongation factors
Summary: Transcription factors whose primary function is to regulate the rate in which RNA is transcribed.
- Evans R, Blaha G, Bailey S, Steitz T. The structure of LepA, the ribosomal back translocase. Proc Natl Acad Sci U S A. 2008;105:4673-8 pubmed publisher..In this model, the very electrostatically positive CTD of LepA is placed in the direct vicinity of the A site of the large ribosomal subunit, suggesting a possible interaction between the CTD and the back translocated tRNA or 23S rRNA. ..
- Heo K, Kim H, Choi S, Choi J, Kim K, Gu J, et al. FACT-mediated exchange of histone variant H2AX regulated by phosphorylation of H2AX and ADP-ribosylation of Spt16. Mol Cell. 2008;30:86-97 pubmed publisher..Thus, these data establish FACT as the major regulator involved in H2AX exchange process that is modulated by H2AX phosphorylation and Spt16 ADP-ribosylation. ..
- Ghavi Helm Y, Michaut M, Acker J, Aude J, Thuriaux P, Werner M, et al. Genome-wide location analysis reveals a role of TFIIS in RNA polymerase III transcription. Genes Dev. 2008;22:1934-47 pubmed publisher..In vitro transcription assays suggested that TFIIS may affect Pol III start site selection. These data provide strong in vivo and in vitro evidence in favor of a role of TFIIS as a general Pol III transcription factor. ..
- Bennett C, Westmoreland T, Verrier C, Blanchette C, Sabin T, Phatnani H, et al. Yeast screens identify the RNA polymerase II CTD and SPT5 as relevant targets of BRCA1 interaction. PLoS ONE. 2008;3:e1448 pubmed publisher..These results extend the mechanistic links between BRCA1 and transcriptional consequences in response to DNA damage and suggest an important role for RNAPII P-CTD cleavage in BRCA1-mediated cancer suppression. ..
- O Donnell A, Stevens J, Kepkay R, Barnes C, Johnston G, Singer R. New mutant versions of yeast FACT subunit Spt16 affect cell integrity. Mol Genet Genomics. 2009;282:487-502 pubmed publisher..Thus, the FACT subunit Spt16 and Pkc1 signaling have an overlapping essential function, with an unexpected role for FACT in the maintenance of cell integrity. ..
- Tsunaka Y, Toga J, Yamaguchi H, Tate S, Hirose S, Morikawa K. Phosphorylated intrinsically disordered region of FACT masks its nucleosomal DNA binding elements. J Biol Chem. 2009;284:24610-21 pubmed publisher..Importantly, this control mechanism appears to support rapid chromatin transactions during early embryogenesis through the dephosphorylation of some sites in the maternally transmitted dSSRP1. ..
- Krishnan K, Salomonis N, Guo S. Identification of Spt5 target genes in zebrafish development reveals its dual activity in vivo. PLoS ONE. 2008;3:e3621 pubmed publisher..Together our findings establish Spt5 as a dual regulator of transcription elongation in vivo and identify a small but diverse set of target genes critically dependent on Spt5 during development. ..
- Svejstrup J. Elongator complex: how many roles does it play?. Curr Opin Cell Biol. 2007;19:331-6 pubmed..One of the subunits of Elongator is encoded by a gene that is mutated in patients suffering from the severe neurodevelopmental disorder familial dysautonomia. ..
- Rutherford S, Lemke J, Vrentas C, Gaal T, Ross W, Gourse R. Effects of DksA, GreA, and GreB on transcription initiation: insights into the mechanisms of factors that bind in the secondary channel of RNA polymerase. J Mol Biol. 2007;366:1243-57 pubmed..Our results provide important clues to the mechanisms of both negative and positive control of transcription initiation by DksA. ..
- Rodriguez Gil A, García Martínez J, Pelechano V, Muñoz Centeno M, Geli V, Pérez Ortín J, et al. The distribution of active RNA polymerase II along the transcribed region is gene-specific and controlled by elongation factors. Nucleic Acids Res. 2010;38:4651-64 pubmed publisher..We conducted a more detailed investigation of the alterations caused by rpb9Delta to find that Rpb9 contributes to the intragenic profiles of active transcription by influencing the probability of arrest of RNA polymerase II. ..
- Mayer A, Lidschreiber M, Siebert M, Leike K, Söding J, Cramer P. Uniform transitions of the general RNA polymerase II transcription complex. Nat Struct Mol Biol. 2010;17:1272-8 pubmed publisher..Transitions are uniform and independent of gene length, type and expression. ..
- Anderson S, Sikes M, Zhang Y, French S, Salgia S, Beyer A, et al. The transcription elongation factor Spt5 influences transcription by RNA polymerase I positively and negatively. J Biol Chem. 2011;286:18816-24 pubmed publisher..These findings bolster the model that Spt5p and related homologues serve diverse critical roles in the control of transcription. ..
- Shema E, Kim J, Roeder R, Oren M. RNF20 inhibits TFIIS-facilitated transcriptional elongation to suppress pro-oncogenic gene expression. Mol Cell. 2011;42:477-88 pubmed publisher..Our findings provide a molecular mechanism for selective gene repression by RNF20 and position TFIIS as a key target of RNF20's tumor suppressor activity. ..
- Biswas D, Yu Y, Prall M, Formosa T, Stillman D. The yeast FACT complex has a role in transcriptional initiation. Mol Cell Biol. 2005;25:5812-22 pubmed..Thus, yFACT functions in establishing transcription initiation complexes in addition to the previously described role in elongation. ..
- Bartholomeeusen K, Xiang Y, Fujinaga K, Peterlin B. Bromodomain and extra-terminal (BET) bromodomain inhibition activate transcription via transient release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein. J Biol Chem. 2012;287:36609-16 pubmed publisher..Finally, the effects of JQ1 and HMBA or SAHA on the P-TEFb equilibrium were cooperative. We conclude that HMBA, SAHA, and JQ1 affect transcription elongation by a similar and convergent mechanism. ..
- Jennings B. Pausing for thought: disrupting the early transcription elongation checkpoint leads to developmental defects and tumourigenesis. Bioessays. 2013;35:553-60 pubmed publisher..Analysis of these mutations has revealed that control of transcriptional pausing is critical for a diverse range of biological pathways essential for animal development and survival. ..
- Lin C, Smith E, Takahashi H, Lai K, Martin Brown S, Florens L, et al. AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. Mol Cell. 2010;37:429-37 pubmed publisher..Knockdown of AFF4 in leukemic cells shows reduction in MLL chimera target gene expression, suggesting that AFF4/SEC could be a key regulator in the pathogenesis of leukemia through many of the MLL partners. ..
- Kiely C, Marguerat S, Garcia J, Madhani H, Bahler J, Winston F. Spt6 is required for heterochromatic silencing in the fission yeast Schizosaccharomyces pombe. Mol Cell Biol. 2011;31:4193-204 pubmed publisher..Taken together, our results suggest that Spt6 is required for multiple steps in heterochromatic silencing by controlling chromatin, transcriptional, and posttranscriptional processes. ..
- Kumari A, Mazina O, Shinde U, Mazin A, Lu H. A role for SSRP1 in recombination-mediated DNA damage response. J Cell Biochem. 2009;108:508-18 pubmed publisher..Taken together, our data suggest a functional role for SSRP1 in spontaneous and replication-associated DNA damage response by suppressing avoidable HR repair events. ..
- Luo Z, Lin C, Shilatifard A. The super elongation complex (SEC) family in transcriptional control. Nat Rev Mol Cell Biol. 2012;13:543-7 pubmed publisher..Recent studies have shown that the SEC belongs to a larger family of SEC-like complexes, which includes SEC-L2 and SEC-L3, each with distinct gene target specificities. ..
- Wier A, Mayekar M, Heroux A, Arndt K, VanDemark A. Structural basis for Spt5-mediated recruitment of the Paf1 complex to chromatin. Proc Natl Acad Sci U S A. 2013;110:17290-5 pubmed publisher..The structure reveals the basis for recognition of the repeat motif of Spt5, a key player in the recruitment of gene regulatory factors to RNA polymerase II. ..
- Nordick K, Hoffman M, BETZ J, Jaehning J. Direct interactions between the Paf1 complex and a cleavage and polyadenylation factor are revealed by dissociation of Paf1 from RNA polymerase II. Eukaryot Cell. 2008;7:1158-67 pubmed publisher..The lack of this connection helps to explain the defects in 3'-end formation observed in the absence of Paf1. ..
- Kireeva M, Hancock B, Cremona G, Walter W, Studitsky V, Kashlev M. Nature of the nucleosomal barrier to RNA polymerase II. Mol Cell. 2005;18:97-108 pubmed..Our findings establish the crucial role of elongation factors that suppress pol II pausing and backtracking for transcription in the context of chromatin. ..
- Workman J. Nucleosome displacement in transcription. Genes Dev. 2006;20:2009-17 pubmed..It is becoming increasingly clear that the eukaryotic transcriptional machinery is adapted to exploit the presence of nucleosomes in very sophisticated ways. ..
- Borukhov S, Lee J, Laptenko O. Bacterial transcription elongation factors: new insights into molecular mechanism of action. Mol Microbiol. 2005;55:1315-24 pubmed
- Ransom M, Williams S, Dechassa M, Das C, Linger J, Adkins M, et al. FACT and the proteasome promote promoter chromatin disassembly and transcriptional initiation. J Biol Chem. 2009;284:23461-71 pubmed publisher..Finally, we rule out the possibility that the proteasome or ATPase cap is driving chromatin disassembly via a potential ATP-dependent chromatin remodeling activity. ..
- Lin C, Garrett A, De Kumar B, Smith E, Gogol M, Seidel C, et al. Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC). Genes Dev. 2011;25:1486-98 pubmed publisher..Our findings suggest that SEC is a major class of active P-TEFb-containing complexes required for transcriptional activation in response to environmental cues such as differentiation signals. ..
- Pavri R, Zhu B, Li G, Trojer P, Mandal S, Shilatifard A, et al. Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell. 2006;125:703-17 pubmed
- Ding B, Lejeune D, Li S. The C-terminal repeat domain of Spt5 plays an important role in suppression of Rad26-independent transcription coupled repair. J Biol Chem. 2010;285:5317-26 pubmed publisher..Phosphorylation of the Spt5 CTR by the Bur kinase may facilitate the assembly of the suppressor complex. ..
- Liu H, Pan D, Pech M, Cooperman B. Interrupted catalysis: the EF4 (LepA) effect on back-translocation. J Mol Biol. 2010;396:1043-52 pubmed publisher..The delay in polypeptide elongation resulting from transient accumulation of I(3) is likely to be important for optimizing functional protein biosynthesis. ..
- Barboric M, Peterlin B. A new paradigm in eukaryotic biology: HIV Tat and the control of transcriptional elongation. PLoS Biol. 2005;3:e76 pubmed
- Qin Y, Polacek N, Vesper O, Staub E, Einfeldt E, Wilson D, et al. The highly conserved LepA is a ribosomal elongation factor that back-translocates the ribosome. Cell. 2006;127:721-33 pubmed..We suggest renaming LepA as elongation factor 4 (EF4). ..
- Hirtreiter A, Damsma G, Cheung A, Klose D, Grohmann D, Vojnic E, et al. Spt4/5 stimulates transcription elongation through the RNA polymerase clamp coiled-coil motif. Nucleic Acids Res. 2010;38:4040-51 pubmed publisher..Using a mutagenesis approach, we have identified a hydrophobic pocket on the Spt5 NGN domain as binding site for RNAP, and reciprocally the RNAP clamp coiled-coil motif as binding site for Spt4/5...
- St Amour C, Sansó M, Bösken C, Lee K, Larochelle S, Zhang C, et al. Separate domains of fission yeast Cdk9 (P-TEFb) are required for capping enzyme recruitment and primed (Ser7-phosphorylated) Rpb1 carboxyl-terminal domain substrate recognition. Mol Cell Biol. 2012;32:2372-83 pubmed publisher..Therefore, fission yeast Cdk9 comprises a catalytic domain sufficient for primed substrate recognition and a multivalent recruitment module that couples transcription with capping. ..
- Schneider D, French S, Osheim Y, Bailey A, Vu L, Dodd J, et al. RNA polymerase II elongation factors Spt4p and Spt5p play roles in transcription elongation by RNA polymerase I and rRNA processing. Proc Natl Acad Sci U S A. 2006;103:12707-12 pubmed..These data suggest that Spt4p, Spt5p, and, potentially, other regulators of Pol I transcription elongation play important roles in coupling rRNA transcription to its processing and ribosome assembly. ..
- Rickards B, Flint S, Cole M, LeRoy G. Nucleolin is required for RNA polymerase I transcription in vivo. Mol Cell Biol. 2007;27:937-48 pubmed..Knockdown of nucleolin by RNA interference resulted in specific inhibition of RNA polymerase I transcription. We therefore propose that an important function of nucleolin is to permit RNA polymerase I to transcribe nucleolar chromatin. ..
- Imbeault D, Gamar L, Rufiange A, Paquet E, Nourani A. The Rtt106 histone chaperone is functionally linked to transcription elongation and is involved in the regulation of spurious transcription from cryptic promoters in yeast. J Biol Chem. 2008;283:27350-4 pubmed publisher..Taken together, our results indicate a direct link for Rtt106 with transcription elongation and the chromatin dynamics associated with RNA polymerase II passage. ..
- Schneider S, Pei Y, Shuman S, Schwer B. Separable functions of the fission yeast Spt5 carboxyl-terminal domain (CTD) in capping enzyme binding and transcription elongation overlap with those of the RNA polymerase II CTD. Mol Cell Biol. 2010;30:2353-64 pubmed publisher..Viability of yeast cells bearing both Spt5 CTD T1A and Pol II CTD S2A mutations heralds that the Cdk9 kinase has an essential target other than Spt5 and Pol II CTD-Ser2. ..
- Li Y, Zeng S, Landais I, Lu H. Human SSRP1 has Spt16-dependent and -independent roles in gene transcription. J Biol Chem. 2007;282:6936-45 pubmed..These results suggest that SSRP1 has Spt16-dependent and -independent roles in regulating gene transcription in human cells. ..
- Schwabish M, Struhl K. Evidence for eviction and rapid deposition of histones upon transcriptional elongation by RNA polymerase II. Mol Cell Biol. 2004;24:10111-7 pubmed
- Ito T, Arimitsu N, Takeuchi M, Kawamura N, Nagata M, Saso K, et al. Transcription elongation factor S-II is required for definitive hematopoiesis. Mol Cell Biol. 2006;26:3194-203 pubmed..Thus, S-II has critical and nonredundant roles in definitive hematopoiesis. ..
- Smith E, Lin C, Shilatifard A. The super elongation complex (SEC) and MLL in development and disease. Genes Dev. 2011;25:661-72 pubmed publisher..Here, we review the normal developmental roles of MLL and the SEC, and how MLL fusion proteins can mediate leukemogenesis. ..
- Kuhn C, Geiger S, Baumli S, Gartmann M, Gerber J, Jennebach S, et al. Functional architecture of RNA polymerase I. Cell. 2007;131:1260-72 pubmed..In contrast to Pol II, Pol I has a strong intrinsic 3'-RNA cleavage activity, which requires the C-terminal domain of subunit A12.2 and, apparently, enables ribosomal RNA proofreading and 3'-end trimming. ..
- Pelechano V, Jimeno González S, Rodriguez Gil A, García Martínez J, Pérez Ortín J, Chávez S. Regulon-specific control of transcription elongation across the yeast genome. PLoS Genet. 2009;5:e1000614 pubmed publisher..This work demonstrates that the regulation of transcription elongation is a widespread, gene class-dependent phenomenon that also affects housekeeping genes. ..
- Myers C, Berner G, Holthoff J, Martinez Fonts K, Harper J, Alford S, et al. Mutant versions of the S. cerevisiae transcription elongation factor Spt16 define regions of Spt16 that functionally interact with histone H3. PLoS ONE. 2011;6:e20847 pubmed publisher..Taken together, our studies point to previously undescribed roles for the Spt16 M-domain and extreme carboxy terminus in regulating interactions between Spt16 and chromatin during the process of transcription elongation. ..
- Xin H, Takahata S, Blanksma M, McCullough L, Stillman D, Formosa T. yFACT induces global accessibility of nucleosomal DNA without H2A-H2B displacement. Mol Cell. 2009;35:365-76 pubmed publisher..We propose that yFACT promotes a reversible transition between two nucleosomal forms, and that this activity contributes to the establishment and maintenance of the chromatin barrier as well as to overcoming it. ..
- O Donnell A, Brewster N, Kurniawan J, Minard L, Johnston G, Singer R. Domain organization of the yeast histone chaperone FACT: the conserved N-terminal domain of FACT subunit Spt16 mediates recovery from replication stress. Nucleic Acids Res. 2004;32:5894-906 pubmed..Genetic interactions suggest that some functions carried out by the Spt16 NTD may be partially redundant within FACT. ..
- ..quot; The structures of two domains of FACT have been determined and they reveal multiple potential interaction sites. Roles for these binding sites in FACT function and regulation are discussed. ..
- Zeng S, Li Y, Jin Y, Zhang Q, Keller D, McQuaw C, et al. Structure-specific recognition protein 1 facilitates microtubule growth and bundling required for mitosis. Mol Cell Biol. 2010;30:935-47 pubmed publisher..These results demonstrate that SSRP1 is crucial for MT growth and spindle assembly during mitosis. ..
- Wang D, Bushnell D, Huang X, Westover K, Levitt M, Kornberg R. Structural basis of transcription: backtracked RNA polymerase II at 3.4 angstrom resolution. Science. 2009;324:1203-6 pubmed publisher..Structure determination of a cocrystal with TFIIS reveals a rearrangement whereby cleavage of the RNA may take place. ..