Evidence map›Paper›PMID 26590638›Full record

ArticleChemistry & biology2015

Optogenetic Inhibitor of the Transcription Factor CREB.

Ahmed M Ali, Jakeb M Reis, Yan Xia, Asim J Rashid, Valentina Mercaldo, Brandon J Walters, Katherine E Brechun, Vitali Borisenko, Sheena A Josselyn, John Karanicolas and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

20 citing papers in PubMed, 41 citations in OpenAlex.

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  16. Molecular Mechanisms of the Memory Trace.Trends in neurosciences · 2019
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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

11 authors at 2 institutions in 3 countries.

Ahmed M AliDepartment of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada; Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt.
Jakeb M ReisDepartment of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada.
Yan XiaDepartment of Molecular Biosciences, and Center for Computational Biology, University of Kansas, Lawrence, KS 66045, USA.
Asim J RashidProgram in Neurosciences & Mental Health at The Hospital for Sick Children, and Departments of Psychology and Physiology and the Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X8, Canada.
Valentina MercaldoProgram in Neurosciences & Mental Health at The Hospital for Sick Children, and Departments of Psychology and Physiology and the Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X8, Canada.
Brandon J WaltersProgram in Neurosciences & Mental Health at The Hospital for Sick Children, and Departments of Psychology and Physiology and the Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X8, Canada.
Katherine E BrechunDepartment of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada.
Vitali BorisenkoDepartment of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada.
Sheena A JosselynProgram in Neurosciences & Mental Health at The Hospital for Sick Children, and Departments of Psychology and Physiology and the Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X8, Canada.
John KaranicolasDepartment of Molecular Biosciences, and Center for Computational Biology, University of Kansas, Lawrence, KS 66045, USA.
G Andrew WoolleyDepartment of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada. Electronic address: awoolley@chem.utoronto.ca.
University of Toronto · CAUniversity of Kansas · US

Funding

Photo-chemical tools for manipulating neural plasticityR01MH086379 · NIMH · UNIVERSITY OF TORONTO · PI WOOLLEY, ANDREW · 2009 to 2012
$667k
NIMH NIH HHS R01 MH086379
6 · The paper itself

Abstract

Current approaches for optogenetic control of transcription do not mimic the activity of endogenous transcription factors, which act at numerous sites in the genome in a complex interplay with other factors. Optogenetic control of dominant negative versions of endogenous transcription factors provides a mechanism for mimicking the natural regulation of gene expression. Here we describe opto-DN-CREB, a blue-light-controlled inhibitor of the transcription factor CREB created by fusing the dominant negative inhibitor A-CREB to photoactive yellow protein (PYP). A light-driven conformational change in PYP prevents coiled-coil formation between A-CREB and CREB, thereby activating CREB. Optogenetic control of CREB function was characterized in vitro, in HEK293T cells, and in neurons where blue light enabled control of expression of the CREB targets NR4A2 and c-Fos. Dominant negative inhibitors exist for numerous transcription factors; linking these to optogenetic domains offers a general approach for spatiotemporal control of native transcriptional events.

Indexed as

OptogeneticsBacterial ProteinsCoumaric AcidsCREB-Binding ProteinDNAElectrophoretic Mobility Shift AssayHEK293 CellsHumansLightNuclear Receptor Subfamily 4, Group A, Member 2Photoreceptors, MicrobialPropionatesProtein BindingProto-Oncogene Proteins c-fosBacterial ProteinsCoumaric AcidsCREB-Binding ProteinCREBBP protein, humanDNANR4A2 protein, humanNuclear Receptor Subfamily 4, Group A, Member 2p-coumaric acidphotoactive yellow protein, BacteriaPhotoreceptors, MicrobialPropionatesProto-Oncogene Proteins c-fosCREBdominant negativeendogenousgenetically encodedoptogeneticsphotoactive yellow proteinphoto-controlphotoisomerizationPYPtranscription factor

Identifiers

PMID26590638
PMCPMC4656143
OpenAlexW2175428656

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.