Evidence map›Paper›PMID 28369554›Full record

ArticleNucleic acids research2017

The haploinsufficient tumor suppressor, CUX1, acts as an analog transcriptional regulator that controls target genes through distal enhancers that loop to target promoters.

Robert K Arthur, Ningfei An, Saira Khan, Megan E McNerney

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

16 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
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  4. Article
  5. Article
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  8. Article
  9. Haploinsufficient tumor suppressor PRP4K is negatively regulated during epithelial-to-mesenchymal transition.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
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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

4 authors at 1 institution in 1 country.

Robert K ArthurDepartment of Pathology, Department of Pediatrics, Section of Hematology/Oncology, and The University of Chicago Medicine Comprehensive Cancer Center, The University of Chicago, Chicago, IL 60637, USA.
Ningfei AnDepartment of Pathology, Department of Pediatrics, Section of Hematology/Oncology, and The University of Chicago Medicine Comprehensive Cancer Center, The University of Chicago, Chicago, IL 60637, USA.
Saira KhanDepartment of Pathology, Department of Pediatrics, Section of Hematology/Oncology, and The University of Chicago Medicine Comprehensive Cancer Center, The University of Chicago, Chicago, IL 60637, USA.
Megan E McNerneyDepartment of Pathology, Department of Pediatrics, Section of Hematology/Oncology, and The University of Chicago Medicine Comprehensive Cancer Center, The University of Chicago, Chicago, IL 60637, USA.
University of Chicago · US

Funding

Determining the role of CUX1 in myeloid neoplasiaK08CA181254 · NCI · UNIVERSITY OF CHICAGO · PI MCNERNEY, MEGAN · 2014 to 2018
$846k
NCI NIH HHS K08 CA181254
6 · The paper itself

Abstract

One third of tumor suppressors are haploinsufficient transcriptional regulators, yet it remains unknown how a 50% reduction of a transcription factor is translated at the cis-regulatory level into a malignant transcriptional program. We studied CUX1, a haploinsufficient transcription factor that is recurrently mutated in hematopoietic and solid tumors. We determined CUX1 DNA-binding and target gene regulation in the wildtype and haploinsufficient states. CUX1 binds with transcriptional activators and cohesin at distal enhancers across three different human cell types. Haploinsufficiency of CUX1 altered the expression of a large number of genes, including cell cycle regulators, with concomitant increased cellular proliferation. Surprisingly, CUX1 occupancy decreased genome-wide in the haploinsufficient state, and binding site affinity did not correlate with differential gene expression. Instead, differentially expressed genes had multiple, low-affinity CUX1 binding sites, features of analog gene regulation. A machine-learning algorithm determined that chromatin accessibility, enhancer activity, and distance to the transcription start site are features of dose-sensitive CUX1 transcriptional regulation. Moreover, CUX1 is enriched at sites of DNA looping, as determined by Hi-C analysis, and these loops connect CUX1 to the promoters of regulated genes. We propose an analog model for haploinsufficient transcriptional deregulation mediated by higher order genome architecture.

Indexed as

Enhancer Elements, GeneticPromoter Regions, GeneticTranscription, GeneticBase SequenceCell Cycle ProteinsCell SurvivalChromosomal Proteins, Non-HistoneCohesinsConsensus SequenceHaploinsufficiencyHep G2 CellsHomeodomain ProteinsHumansK562 CellsNuclear ProteinsNucleic Acid ConformationCell Cycle ProteinsChromosomal Proteins, Non-HistoneCohesinsCUX1 protein, humanHomeodomain ProteinsNuclear ProteinsRepressor ProteinsTranscription Factors

Identifiers

PMID28369554
PMCPMC5499738
OpenAlexW2601703337

What OpenQuestion holds

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LicenceCC BY-NC
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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.