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Article ; Online: Broad compatibility between yeast UAS elements and core promoters and identification of promoter elements that determine cofactor specificity.

Schofield, Jeremy A / Hahn, Steven

2023 Volume 42, Issue 4, Page(s) 112387

Abstract: Three classes of yeast protein-coding genes are distinguished by their dependence on the transcription cofactors TFIID, SAGA, and Mediator (MED) Tail, but whether this dependence is determined by the core promoter, upstream activating sequences (UASs), ... ...

Abstract	Three classes of yeast protein-coding genes are distinguished by their dependence on the transcription cofactors TFIID, SAGA, and Mediator (MED) Tail, but whether this dependence is determined by the core promoter, upstream activating sequences (UASs), or other gene features is unclear. Also unclear is whether UASs can broadly activate transcription from the different promoter classes. Here, we measure transcription and cofactor specificity for thousands of UAS-core promoter combinations and find that most UASs broadly activate promoters regardless of regulatory class, while few display strong promoter specificity. However, matching UASs and promoters from the same gene class is generally important for optimal expression. We find that sensitivity to rapid depletion of MED Tail or SAGA is dependent on the identity of both UAS and core promoter, while dependence on TFIID localizes to only the promoter. Finally, our results suggest the role of TATA and TATA-like promoter sequences in MED Tail function.
MeSH term(s)	Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Promoter Regions, Genetic/genetics ; Transcription Factor TFIID/genetics ; Transcription Factor TFIID/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Transcription, Genetic ; TATA Box/genetics
Chemical Substances	Transcription Factor TFIID ; Saccharomyces cerevisiae Proteins
Language	English
Publishing date	2023-04-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112387
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Broad compatibility between yeast UAS elements and core promoters and identification of promoter elements that determine cofactor specificity

Jeremy A. Schofield / Steven Hahn

Cell Reports, Vol 42, Iss 4, Pp 112387- (2023)

2023

Abstract: Summary: Three classes of yeast protein-coding genes are distinguished by their dependence on the transcription cofactors TFIID, SAGA, and Mediator (MED) Tail, but whether this dependence is determined by the core promoter, upstream activating sequences ( ...

Abstract	Summary: Three classes of yeast protein-coding genes are distinguished by their dependence on the transcription cofactors TFIID, SAGA, and Mediator (MED) Tail, but whether this dependence is determined by the core promoter, upstream activating sequences (UASs), or other gene features is unclear. Also unclear is whether UASs can broadly activate transcription from the different promoter classes. Here, we measure transcription and cofactor specificity for thousands of UAS-core promoter combinations and find that most UASs broadly activate promoters regardless of regulatory class, while few display strong promoter specificity. However, matching UASs and promoters from the same gene class is generally important for optimal expression. We find that sensitivity to rapid depletion of MED Tail or SAGA is dependent on the identity of both UAS and core promoter, while dependence on TFIID localizes to only the promoter. Finally, our results suggest the role of TATA and TATA-like promoter sequences in MED Tail function.
Keywords	upstream activating sequences (UASs) ; enhancers ; core promoters ; transcriptional coactivators ; large-scale reporter ; mediator ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Improving the study of RNA dynamics through advances in RNA-seq with metabolic labeling and nucleotide-recoding chemistry.

Zimmer, Joshua T / Vock, Isaac W / Schofield, Jeremy A / Kiefer, Lea / Moon, Michelle H / Simon, Matthew D

bioRxiv : the preprint server for biology

2023

Abstract: RNA metabolic labeling using 4-thiouridine ( ... ...

Abstract	RNA metabolic labeling using 4-thiouridine (s
Language	English
Publishing date	2023-05-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.24.542133
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Article ; Online: Global Profiling of Cellular Substrates of Human Dcp2.

Luo, Yang / Schofield, Jeremy A / Simon, Matthew D / Slavoff, Sarah A

Biochemistry

2020 Volume 59, Issue 43, Page(s) 4176–4188

Abstract: Decapping is the first committed step in 5'-to-3' RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of distinct subsets of cellular transcripts. However, the complete set of RNAs regulated by any ... ...

Abstract	Decapping is the first committed step in 5'-to-3' RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of distinct subsets of cellular transcripts. However, the complete set of RNAs regulated by any individual decapping enzyme remains incompletely mapped, and no consensus sequence or property is currently known to unambiguously predict decapping enzyme substrates. Dcp2 was the first-identified and best-studied eukaryotic decapping enzyme, but it has been shown to regulate the stability of <400 transcripts in mammalian cells to date. Here, we globally profile changes in the stability of the human transcriptome in Dcp2 knockout cells via TimeLapse-seq. We find that P-body enrichment is the strongest correlate of Dcp2-dependent decay and that modification with m
MeSH term(s)	Animals ; Cytoplasm/genetics ; Cytoplasm/metabolism ; Endoribonucleases/genetics ; Endoribonucleases/metabolism ; Humans ; Models, Biological ; RNA Stability/genetics ; RNA Stability/physiology ; Transcriptome/genetics ; Transcriptome/physiology
Chemical Substances	Endoribonucleases (EC 3.1.-) ; DCP2 protein, human (EC 3.1.27.-)
Language	English
Publishing date	2020-05-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/acs.biochem.0c00069
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Article ; Online: Expanding the Nucleoside Recoding Toolkit: Revealing RNA Population Dynamics with 6-Thioguanosine.

Kiefer, Lea / Schofield, Jeremy A / Simon, Matthew D

Journal of the American Chemical Society

2018 Volume 140, Issue 44, Page(s) 14567–14570

Abstract: RNA-sequencing (RNA-seq) measures RNA abundance in a biological sample but does not provide temporal information about the sequenced RNAs. Metabolic labeling can be used to distinguish newly made RNAs from pre-existing RNAs. Mutations induced from ... ...

Abstract	RNA-sequencing (RNA-seq) measures RNA abundance in a biological sample but does not provide temporal information about the sequenced RNAs. Metabolic labeling can be used to distinguish newly made RNAs from pre-existing RNAs. Mutations induced from chemical recoding of the hydrogen bonding pattern of the metabolic label can reveal which RNAs are new in the context of a sequencing experiment. These nucleotide recoding strategies have been developed for a single uridine analogue, 4-thiouridine (s
MeSH term(s)	Guanosine/analogs & derivatives ; Guanosine/chemistry ; Guanosine/metabolism ; Hydrogen Bonding ; Nucleosides/chemistry ; Nucleosides/metabolism ; RNA/chemistry ; RNA/metabolism ; Thionucleosides/chemistry ; Thionucleosides/metabolism
Chemical Substances	Nucleosides ; Thionucleosides ; Guanosine (12133JR80S) ; RNA (63231-63-0) ; 6-thioguanosine (C558LI0K8P)
Language	English
Publishing date	2018-10-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.8b08554
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Article ; Online: Gaining insight into transcriptome-wide RNA population dynamics through the chemistry of 4-thiouridine.

Duffy, Erin E / Schofield, Jeremy A / Simon, Matthew D

Wiley interdisciplinary reviews. RNA

2018 Volume 10, Issue 1, Page(s) e1513

Abstract: Cellular RNA levels are the result of a juggling act between RNA transcription, processing, and degradation. By tuning one or more of these parameters, cells can rapidly alter the available pool of transcripts in response to stimuli. While RNA sequencing ...

Abstract	Cellular RNA levels are the result of a juggling act between RNA transcription, processing, and degradation. By tuning one or more of these parameters, cells can rapidly alter the available pool of transcripts in response to stimuli. While RNA sequencing (RNA-seq) is a vital method to quantify RNA levels genome-wide, it is unable to capture the dynamics of different RNA populations at steady-state or distinguish between different mechanisms that induce changes to the steady-state (i.e., altered rate of transcription vs. degradation). The dynamics of different RNA populations can be studied by targeted incorporation of noncanonical nucleosides. 4-Thiouridine (s
MeSH term(s)	Animals ; Humans ; RNA/metabolism ; Thiouridine/metabolism ; Transcriptome
Chemical Substances	Thiouridine (13957-31-8) ; RNA (63231-63-0)
Language	English
Publishing date	2018-10-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2634714-3
ISSN	1757-7012 ; 1757-7004
ISSN (online)	1757-7012
ISSN	1757-7004
DOI	10.1002/wrna.1513
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Article ; Online: The Role of Ambulatory Heart Failure Clinics to Avoid Heart Failure Admissions.

He, Jessica / Balmain, Sean / Kobulnik, Jeremy / Schofield, Anne / Mak, Susanna

CJC open

2019 Volume 2, Issue 1, Page(s) 15–21

Abstract: Background: There is a complex relationship between heart failure (HF) clinic services and health outcomes. We hypothesized that ambulatory clinic activity may be associated with both hospital admission and also with avoidance of admission.: Methods: ...

Abstract	Background: There is a complex relationship between heart failure (HF) clinic services and health outcomes. We hypothesized that ambulatory clinic activity may be associated with both hospital admission and also with avoidance of admission. Methods: A retrospective comparative cohort study was conducted examining activity in an ambulatory HF Clinic. Consecutive clinic visits in 2013 were recorded (n = 1728) and periods of high-intensity utilization (HIU) were identified (n = 128). A HIU period was defined by ≥2 consecutive clinic visits within 30 days, ending after 30 days passed without an additional clinic visit. For each HIU period identified, patient characteristics (n = 107) and all clinic visits (n = 324) were examined. HIU periods were then classified by association with hospital admission (±30 days). Results: In 2013, 18.8% of all clinic visits occurred during HIU periods, involving 13.7% of the clinic population. Thirty-eight percent of HIU periods were associated with 62 total hospital admissions (±30 days), of which 58% (n = 36) were for a primary diagnosis of HF. In addition,17 HIU periods met criteria for admission avoided, and 7 HIU periods occurring after hospital discharge also met criteria for admission avoided. Conclusions: We identified periods of intensive ambulatory clinic activity dedicated to patients with high burdens of comorbidities and both HF and non-HF-related admissions. These periods were also associated with episodes of successful decongestion with oral diuretics, resulting in avoidance of admission. Identifying HF patients who can be treated successfully or who are likely to require admission may be helpful for allocating clinic resources.
Language	English
Publishing date	2019-12-06
Publishing country	United States
Document type	Journal Article
ISSN	2589-790X
ISSN (online)	2589-790X
DOI	10.1016/j.cjco.2019.11.007
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Article ; Online: Discovery of cellular substrates of human RNA-decapping enzyme DCP2 using a stapled bicyclic peptide inhibitor.

Luo, Yang / Schofield, Jeremy A / Na, Zhenkun / Hann, Tanja / Simon, Matthew D / Slavoff, Sarah A

Cell chemical biology

2020 Volume 28, Issue 4, Page(s) 463–474.e7

Abstract: DCP2 is an RNA-decapping enzyme that controls the stability of human RNAs that encode factors functioning in transcription and the immune response. While >1,800 human DCP2 substrates have been identified, compensatory expression changes secondary to ... ...

Abstract	DCP2 is an RNA-decapping enzyme that controls the stability of human RNAs that encode factors functioning in transcription and the immune response. While >1,800 human DCP2 substrates have been identified, compensatory expression changes secondary to genetic ablation of DCP2 have complicated a complete mapping of its regulome. Cell-permeable, selective chemical inhibitors of DCP2 could provide a powerful tool to study DCP2 specificity. Here, we report phage display selection of CP21, a bicyclic peptide ligand to DCP2. CP21 has high affinity and selectivity for DCP2 and inhibits DCP2 decapping activity toward selected RNA substrates in human cells. CP21 increases formation of P-bodies, liquid condensates enriched in intermediates of RNA decay, in a manner that resembles the deletion or mutation of DCP2. We used CP21 to identify 76 previously unreported DCP2 substrates. This work demonstrates that DCP2 inhibition can complement genetic approaches to study RNA decay.
MeSH term(s)	Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis ; Bridged Bicyclo Compounds, Heterocyclic/chemistry ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Drug Discovery ; Endoribonucleases/antagonists & inhibitors ; Endoribonucleases/metabolism ; Enzyme Inhibitors/chemical synthesis ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; HEK293 Cells ; Humans ; Molecular Conformation ; Peptides/chemical synthesis ; Peptides/chemistry ; Peptides/pharmacology
Chemical Substances	Bridged Bicyclo Compounds, Heterocyclic ; Enzyme Inhibitors ; Peptides ; Endoribonucleases (EC 3.1.-) ; DCP2 protein, human (EC 3.1.27.-)
Language	English
Publishing date	2020-12-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2451-9448
ISSN (online)	2451-9448
DOI	10.1016/j.chembiol.2020.12.003
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Article ; Online: Co-designing an online treatment decision aid for men with low-risk prostate cancer: Navigate.

Schofield, Penelope / Hyatt, Amelia / White, Alan / White, Fiona / Frydenberg, Mark / Chambers, Suzanne / Gardiner, Robert / Murphy, Declan G / Cavedon, Lawrence / Millar, Jeremy / Richards, Natalie / Murphy, Barbara / Juraskova, Ilona

BJUI compass

2023 Volume 5, Issue 1, Page(s) 121–141

Abstract: Objectives: To develop an online treatment decision aid (OTDA) to assist patients with low-risk prostate cancer (LRPC) and their partners in making treatment decisions.: Patients and methods: Navigate: Results: The initial workshops identified key ...

Abstract	Objectives: To develop an online treatment decision aid (OTDA) to assist patients with low-risk prostate cancer (LRPC) and their partners in making treatment decisions. Patients and methods: Navigate Results: The initial workshops identified key content and design features that were incorporated into the draft OTDA, re-workshopped and incorporated into the penultimate OTDA. Expert feedback on usability and content was also incorporated into the final OTDA. The final OTDA was deemed comprehensive, clear and appropriate and met all IPDAS criteria. Conclusion: Navigate
Language	English
Publishing date	2023-08-31
Publishing country	United States
Document type	Journal Article
ISSN	2688-4526
ISSN (online)	2688-4526
DOI	10.1002/bco2.279
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Article: Expanding the Nucleoside Recoding Toolkit: Revealing RNA Population Dynamics with 6-Thioguanosine

Kiefer, Lea / Schofield, Jeremy A / Simon, Matthew D

Journal of the American Chemical Society. 2018 Oct. 15, v. 140, no. 44

2018

Abstract	RNA-sequencing (RNA-seq) measures RNA abundance in a biological sample but does not provide temporal information about the sequenced RNAs. Metabolic labeling can be used to distinguish newly made RNAs from pre-existing RNAs. Mutations induced from chemical recoding of the hydrogen bonding pattern of the metabolic label can reveal which RNAs are new in the context of a sequencing experiment. These nucleotide recoding strategies have been developed for a single uridine analogue, 4-thiouridine (s4U), limiting the scope of these experiments. Here we report the first use of nucleoside recoding with a guanosine analogue, 6-thioguanosine (s6G). Using TimeLapse sequencing (TimeLapse-seq), s6G can be recoded under RNA-friendly oxidative nucleophilic-aromatic substitution conditions to produce adenine analogues (substituted 2-aminoadenosines). We demonstrate the first use of s6G recoding experiments to reveal transcriptome-wide RNA population dynamics.
Keywords	RNA ; adenine ; guanosine ; hydrogen bonding ; population dynamics ; sequence analysis ; uridine
Language	English
Dates of publication	2018-1015
Size	p. 14567-14570.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.8b08554
Database	NAL-Catalogue (AGRICOLA)

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