Evidence map›Paper›PMID 33334884›Full record

ArticleThe Journal of biological chemistry

Genome editing demonstrates that the -5 kb Nanog enhancer regulates Nanog expression by modulating RNAPII initiation and/or recruitment.

Puja Agrawal, Steven Blinka, Kirthi Pulakanti, Michael H Reimer, Cary Stelloh, Alison E Meyer, Sridhar Rao

Abstract read
In one paragraph

Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

  1. Article
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  5. Article
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  10. Super-enhancers conserved within placental mammals maintain stem cell pluripotency.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  11. Article
  12. Super-Enhancers and CTCF in Early Embryonic Cell Fate Decisions.Frontiers in cell and developmental biology · 2021
    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

7 authors.

Puja AgrawalDepartment of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Blood Research Institute, Versiti, Milwaukee, Wisconsin, USA.
Steven BlinkaDepartment of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Blood Research Institute, Versiti, Milwaukee, Wisconsin, USA.
Kirthi PulakantiBlood Research Institute, Versiti, Milwaukee, Wisconsin, USA.
Michael H ReimerBlood Research Institute, Versiti, Milwaukee, Wisconsin, USA.
Cary StellohBlood Research Institute, Versiti, Milwaukee, Wisconsin, USA.
Alison E MeyerBlood Research Institute, Versiti, Milwaukee, Wisconsin, USA.
Sridhar RaoDepartment of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Blood Research Institute, Versiti, Milwaukee, Wisconsin, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. Electronic address: sridhar.rao@versiti.org.

Funding

Medical Scientist Training ProgramT32GM080202 · NIGMS · MEDICAL COLLEGE OF WISCONSIN · PI BARBIERI, JOSEPH T, SALZMAN, NITA H · 2010 to 2024
$5.7M
Cohesin Mutations in Acute Myelogenous LeukemiaR01CA204231 · NCI · VERSITI WISCONSIN, INC. · PI RAO, SRIDHAR · 2017 to 2021
$1.9M
Nuclear Architecture-driven Cellular Heterogeneity in Stem Cell and Hematopoietic DifferentiationF30DK120152 · NIDDK · VERSITI WISCONSIN, INC. · PI AGRAWAL, PUJA · 2018 to 2021
$198k
NCI NIH HHS R01 CA204231NIDDK NIH HHS F30 DK120152NIGMS NIH HHS T32 GM080202
6 · The paper itself

Abstract

Transcriptional enhancers have been defined by their ability to operate independent of distance and orientation in plasmid-based reporter assays of gene expression. At present, histone marks are used to identify and define enhancers but do not consider the endogenous role of an enhancer in the context of native chromatin. We employed a combination of genomic editing, single cell analyses, and sequencing approaches to investigate a Nanog-associated cis-regulatory element, which has been reported by others to be either an alternative promoter or a super-enhancer. We first demonstrate both distance and orientation independence in native chromatin, eliminating the issues raised with plasmid-based approaches. We next demonstrate that the dominant super-enhancer modulates Nanog globally and operates by recruiting and/or initiating RNA Polymerase II. Our studies have important implications to how transcriptional enhancers are defined and how they regulate gene expression.

Indexed as

AnimalsCell LineCRISPR-Cas SystemsEnhancer Elements, GeneticGene EditingGene Expression RegulationMiceMouse Embryonic Stem CellsNanog Homeobox ProteinRNA Polymerase IITranscriptional ActivationNanog Homeobox ProteinNanog protein, mouseRNA Polymerase IIembryonic stem cellsenhancersgene expressiongene regulationNanogpluripotencysuper-enhancerstranscription regulation

Identifiers

PMID33334884
PMCPMC7948488

What OpenQuestion holds

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LicenceCC BY
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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.