Evidence map›Paper›PMID 33980985›Full record

ArticleCommunications biology2021

CRISPRi-mediated functional analysis of NKX2-1-binding sites in the lung.

William D Stuart, Iris M Fink-Baldauf, Koichi Tomoshige, Minzhe Guo, Yutaka Maeda

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2021. 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
1.8field-weighted citation impact, top 15% 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, 28 citations in OpenAlex.

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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

5 authors at 1 institution in 3 countries.

William D Stuart *Perinatal Institute, Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (CCHMC and UC), Cincinnati, OH, USA.
Iris M Fink-Baldauf *Perinatal Institute, Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (CCHMC and UC), Cincinnati, OH, USA.
Koichi TomoshigePerinatal Institute, Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (CCHMC and UC), Cincinnati, OH, USA.
Minzhe GuoPerinatal Institute, Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (CCHMC and UC), Cincinnati, OH, USA.
Yutaka MaedaPerinatal Institute, Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (CCHMC and UC), Cincinnati, OH, USA. yutaka.maeda@cchmc.org.ORCID 0000-0002-9537-3971
Cincinnati Children's Hospital Medical Center · US

Funding

Editing Alveolar Progenitor Cells for Correction of Monogenic DiseaseU01HL134745 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI KOTTON, DARRELL N., MORRISEY, EDWARD E · 2016 to 2022
$8.3M
Patho-Genetic Analysis of Invasive Mucinous Adenocarcinoma of the LungR01CA240317 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI MAEDA, YUTAKA, SNYDER, ERIC LEE · 2020 to 2024
$3.1M
NCI NIH HHS R01 CA240317NHLBI NIH HHS U01 HL134745
6 · The paper itself

Abstract

The transcription factor NKX2-1/TTF-1 is involved in lung pathophysiology, including breathing, innate defense and tumorigenesis. To understand the mechanism by which NKX2-1 regulates genes involved in such pathophysiology, we have previously performed ChIP-seq and identified genome-wide NKX2-1-binding sites, which revealed that NKX2-1 binds to not only proximal promoter regions but also multiple intra- and inter-genic regions of the genes regulated by NKX2-1. However, the roles of such regions, especially non-proximal ones, bound by NKX2-1 have not yet been determined. Here, using CRISPRi (CRISPR/dCas9-KRAB), we scrutinize the functional roles of 19 regions/sites bound by NKX2-1, which are located in genes involved in breathing and innate defense (SFTPB, LAMP3, SFTPA1, SFTPA2) and lung tumorigenesis (MYBPH, LMO3, CD274/PD-L1). Notably, the CRISPRi approach reveals that a portion of NKX2-1-binding sites are functionally indispensable while the rest are dispensable for the expression of the genes, indicating that functional roles of NKX2-1-binding sites are unequally yoked.

Indexed as

Binding SitesCell Line, TumorCell Transformation, NeoplasticChromatin Immunoprecipitation SequencingCRISPR-Cas SystemsGene Expression Regulation, NeoplasticGenetic EngineeringHumansLungLung NeoplasmsNuclear ProteinsPromoter Regions, GeneticProtein BindingThyroid Nuclear Factor 1Transcription FactorsNKX2-1 protein, humanNuclear ProteinsThyroid Nuclear Factor 1Transcription Factors

Identifiers

PMID33980985
PMCPMC8115294
OpenAlexW3163774004

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.