| 1. |
- Mercuri, E., et al.
(författare)
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Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
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Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
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| 2. |
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| 3. |
- Hoencamp, Claire, et al.
(författare)
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3D genomics across the tree of life reveals condensin II as a determinant of architecture type
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 372:6545, s. 984-989
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Tidskriftsartikel (refereegranskat)abstract
- We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes.
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| 4. |
- Li, Y, et al.
(författare)
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Yeast global transcriptional regulators Sin4 and Rgr1 are components of mediator complex/RNA polymerase II holoenzyme.
- 1995
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 92:24, s. 10864-8
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Tidskriftsartikel (refereegranskat)abstract
- Sin4 and Rgr1 proteins, previously shown by genetic studies to play both positive and negative roles in the transcriptional regulation of many genes, are identified here as components of mediator and RNA polymerase II holoenzyme complexes. Results with Sin4 deletion and Rgr1 truncation strains indicate the association of these proteins in a subcomplex comprising Sin4, Rgr1, Gal11, and a 50-kDa polypeptide. Taken together with the previous genetic evidence, our findings point to a role of the mediator in repression as well as in transcriptional activation.
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| 5. |
- Poon, D, et al.
(författare)
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Identification and characterization of a TFIID-like multiprotein complex from Saccharomyces cerevisiae.
- 1995
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 92:18, s. 8224-8
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Tidskriftsartikel (refereegranskat)abstract
- Although the mechanisms of transcriptional regulation by RNA polymerase II are apparently highly conserved from yeast to man, the identification of a yeast TATA-binding protein (TBP)-TBP-associated factor (TAFII) complex comparable to the metazoan TFIID component of the basal transcriptional machinery has remained elusive. Here, we report the isolation of a yeast TBP-TAFII complex which can mediate transcriptional activation by GAL4-VP16 in a highly purified yeast in vitro transcription system. We have cloned and sequenced the genes encoding four of the multiple yeast TAFII proteins comprising the TBP-TAFII multisubunit complex and find that they are similar at the amino acid level to both human and Drosophila TFIID subunits. Using epitope-tagging and immunoprecipitation experiments, we demonstrate that these genes encode bona fide TAF proteins and show that the yeast TBP-TAFII complex is minimally composed of TBP and seven distinct yTAFII proteins ranging in size from M(r) = 150,000 to M(r) = 25,000. In addition, by constructing null alleles of the cloned TAF-encoding genes, we show that normal function of the TAF-encoding genes is essential for yeast cell viability.
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| 6. |
- Kim, Y J, et al.
(författare)
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A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II.
- 1994
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Ingår i: Cell. - 0092-8674 .- 1097-4172. ; 77:4, s. 599-608
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Tidskriftsartikel (refereegranskat)abstract
- A mediator was isolated from yeast that enabled a response to the activator proteins GAL4-VP16 and GCN4 in a transcription system reconstituted with essentially homogeneous basal factors and RNA polymerase II. The mediator comprised some 20 polypeptides, including the three subunits of TFIIF and other polypeptides cross-reactive with antisera against GAL11, SUG1, SRB2, SRB4, SRB5, and SRB6 proteins. Mediator not only enabled activated transcription but also conferred 8-fold greater activity in basal transcription and 12-fold greater efficiency of phosphorylation of RNA polymerase II by the TFIIH-associated C-terminal repeat domain (CTD) kinase, indicative of mediator-CTD interaction. A holoenzyme form of RNA polymerase II was independently isolated that supported a response to activator proteins with purified basal factors. The holoenzyme proved to consist of mediator associated with core 12-subunit RNA polymerase II.
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| 7. |
- Li, Y, et al.
(författare)
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Yeast RNA polymerase II holoenzyme.
- 1996
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Ingår i: Methods in Enzymology. - 0076-6879 .- 1557-7988. ; 273, s. 172-5
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Tidskriftsartikel (refereegranskat)
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