Evidence map›Paper›PMID 31628195›Full record

ArticleThe Journal of biological chemistry2019

Differential and overlapping targets of the transcriptional regulators NRF1, NRF2, and NRF3 in human cells.

Pengfei Liu, Michael J Kerins, Wang Tian, Durga Neupane, Donna D Zhang, Aikseng Ooi

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

62 citing papers in PubMed, 78 citations in OpenAlex.

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  17. The Ancestral KEAP1-NRF Pathway in AmphioxusInternational journal of molecular sciences · 2025
    Article
  18. Review
  19. Review
  20. Article

2 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Pengfei LiuDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona 85721.
Michael J KerinsDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona 85721.
Wang TianDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona 85721.
Durga NeupaneDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona 85721.
Donna D ZhangDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona 85721; University of Arizona Cancer Center, University of Arizona, Tucson, Arizona 85721.
Aikseng OoiDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona 85721; University of Arizona Cancer Center, University of Arizona, Tucson, Arizona 85721. Electronic address: dzhang@pharmacy.arizona.edu.
University of Arizona · US

Funding

TRANSPORT OF TRACE METALS IN A POLLUTED AQUIFERP42ES004940 · NIEHS · UNIVERSITY OF ARIZONA · PI Xinxin Ding · 1990 to 2026
$68.1M
SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI DEAN BILLHEIMER · 1994 to 2026
$36.7M
Selective Killing of FH-/- Cancer Cells by Targeting Cellular Iron HomeostasisR01CA226920 · NCI · UNIVERSITY OF ARIZONA · PI OOI, AIKSENG · 2019 to 2023
$1.6M
Arsenic, Nrf2 and Autophagy Dysfunction in Type II DiabetesR01DK109555 · NIDDK · UNIVERSITY OF ARIZONA · PI ZHANG, DONNA D · 2016 to 2019
$1.4M
Nrf2, autophagy, and arsenic carcinogenesisR01ES026845 · NIEHS · UNIVERSITY OF ARIZONA · PI ZHANG, DONNA D · 2016 to 2019
$1.4M
Genome Wide CRISPR Screen for Proteins That Transduce Environmental Exposure Signals to the NRF2 PathwayR21ES027920 · NIEHS · UNIVERSITY OF ARIZONA · PI OOI, AIKSENG · 2018 to 2019
$422k
NCI NIH HHS R01 CA226920NIDDK NIH HHS R01 DK109555NIEHS NIH HHS P30 ES006694NIEHS NIH HHS P42 ES004940NIEHS NIH HHS R01 ES026845NIEHS NIH HHS R21 ES027920
6 · The paper itself

Abstract

The nuclear factor (erythroid 2)-like (NRF) transcription factors are a subset of cap'n'collar transcriptional regulators. They consist of three members, NRF1, NRF2, and NRF3, that regulate the expression of genes containing antioxidant-response elements (AREs) in their promoter regions. Although all NRF members regulate ARE-containing genes, each is associated with distinct roles. A comprehensive study of differential and overlapping DNA-binding and transcriptional activities of the NRFs has not yet been conducted. Here, we performed chromatin immunoprecipitation (ChIP)-exo sequencing, an approach that combines ChIP with exonuclease treatment to pinpoint regulatory elements in DNA with high precision, in conjunction with RNA-sequencing to define the transcriptional targets of each NRF member. Our approach, done in three U2OS cell lines, identified 31 genes that were regulated by all three NRF members, 27 that were regulated similarly by all three, and four genes that were differentially regulated by at least one NRF member. We also found genes that were up- or down-regulated by only one NRF member, with 84, 84, and 22 genes that were regulated by NRF1, NRF2, and NRF3, respectively. Analysis of the ARE motifs identified in ChIP peaks revealed that NRF2 prefers binding to AREs flanked by GC-rich regions and that NRF1 prefers AT-rich flanking regions. Thus, sequence preference, likely in combination with upstream signaling events, determines NRF member activation under specific cellular contexts. Our analysis provides a comprehensive description of differential and overlapping gene regulation by the transcriptional regulators NRF1, NRF2, and NRF3.

Indexed as

Gene Expression RegulationBasic-Leucine Zipper Transcription FactorsCell LineHumansNF-E2-Related Factor 1NF-E2-Related Factor 2Nuclear Respiratory Factor 1Basic-Leucine Zipper Transcription FactorsNFE2L1 protein, humanNFE2L2 protein, humanNFE2L3 protein, humanNF-E2-Related Factor 1NF-E2-Related Factor 2NRF1 protein, humanNuclear Respiratory Factor 1antioxidantcell culturecell signalingChIP-sequencing (ChIP-seq)DNA transcriptiongene transcriptionnuclear factor 2 (erythroid-derived 2-like factor) (NFE2L2) (Nrf2)oxidative stresssignal transductiontranscriptomics

Identifiers

PMID31628195
PMCPMC6885608
OpenAlexW2981045331

What OpenQuestion holds

Textmetadata
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.