Evidence map›Paper›PMID 29309117›Full record

ArticleACS chemical biology2018

Chemical Control of a CRISPR-Cas9 Acetyltransferase.

Jonathan H Shrimp, Carissa Grose, Stephanie R T Widmeyer, Abigail L Thorpe, Ajit Jadhav, Jordan L Meier

Abstract read
In one paragraph

Article in ACS chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Chemical and Light Inducible Epigenome Editing.International journal of molecular sciences · 2020
    Review
  10. Cell Reprogramming With CRISPR/Cas9 Based Transcriptional Regulation Systems.Frontiers in bioengineering and biotechnology · 2020
    Review
  11. Article
  12. CRISPR-Cas-Mediated Chemical Control of Transcriptional Dynamics in Yeast.Chembiochem : a European journal of chemical biology · 2019
    Article
  13. Review
  14. Transgenic Mouse Models in Cancer Research.Frontiers in oncology · 2018
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Jonathan H ShrimpChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland 21702, United States.
Carissa GroseProtein Expression Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc. , Frederick, Maryland 21702, United States.
Stephanie R T WidmeyerProtein Expression Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc. , Frederick, Maryland 21702, United States.
Abigail L ThorpeChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland 21702, United States.
Ajit JadhavDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health , Rockville, Maryland 20850, United States.
Jordan L MeierChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland 21702, United States.ORCID 0000-0002-0537-7101
National Institutes of Health · USLeidos (United States) · US

Funding

Targeting Cancer Through Modifications and MetabolismZIABC011488 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MEIER, JORDAN L · 2013 to 2025
$21.3M
CCR NIH HHS HHSN261200800001CIntramural NIH HHS ZIA BC011488NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

Lysine acetyltransferases (KATs) play a critical role in the regulation of transcription and other genomic functions. However, a persistent challenge is the development of assays capable of defining KAT activity directly in living cells. Toward this goal, here we report the application of a previously reported dCas9-p300 fusion as a transcriptional reporter of KAT activity. First, we benchmark the activity of dCas9-p300 relative to other dCas9-based transcriptional activators and demonstrate its compatibility with second generation short guide RNA architectures. Next, we repurpose this technology to rapidly identify small molecule inhibitors of acetylation-dependent gene expression. These studies validate a recently reported p300 inhibitor chemotype and reveal a role for p300s bromodomain in dCas9-p300-mediated transcriptional activation. Comparison with other CRISPR-Cas9 transcriptional activators highlights the inherent ligand tunable nature of dCas9-p300 fusions, suggesting new opportunities for orthogonal gene expression control. Overall, our studies highlight dCas9-p300 as a powerful tool for studying gene expression mechanisms in which acetylation plays a causal role and provide a foundation for future applications requiring spatiotemporal control over acetylation at specific genomic loci.

Indexed as

AcetylationAzepinesBenzimidazolesCapsid ProteinsCRISPR-Associated Protein 9CRISPR-Associated ProteinsCRISPR-Cas SystemsCytomegalovirusE1A-Associated p300 ProteinEnzyme InhibitorsHEK293 CellsHumansHydantoinsInterleukin 1 Receptor Antagonist ProteinIsoxazolesProtein DomainsAzepinesBenzimidazolesCapsid ProteinsCas9 endonuclease Streptococcus pyogenesCBP30 compoundCRISPR-Associated Protein 9CRISPR-Associated ProteinsE1A-Associated p300 ProteinEnzyme InhibitorsEP300 protein, humanHydantoinsIL1RN protein, humanInterleukin 1 Receptor Antagonist ProteinIsoxazoles(+)-JQ1 compoundRecombinant Fusion ProteinsRNA, Guide, CRISPR-Cas SystemsSpiro CompoundsTriazoles

Identifiers

PMID29309117
PMCPMC6320253
OpenAlexW2748423437

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.