Evidence map›Paper›PMID 26631571›Full record

ArticleScientific reports2015

TET-catalyzed 5-hydroxymethylcytosine regulates gene expression in differentiating colonocytes and colon cancer.

Christopher G Chapman, Christopher J Mariani, Feng Wu, Katherine Meckel, Fatma Butun, Alice Chuang, Jozef Madzo, Marc B Bissonnette, John H Kwon, Lucy A Godley

Erratum issued Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03336554 (Indentifying Epigenetic Biomarkers From Peripheral Blood of Osteosarcoma Patients Based on hMe-Seal Technique), which is not on this map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% 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.

NCT03336554 unknown statusnot on this mapstarted 2017, after this paper: background citation

Indentifying Epigenetic Biomarkers From Peripheral Blood of Osteosarcoma Patients Based on hMe-Seal Technique

Typeobservational_patient_registrySponsorPeking University People's HospitalRan2017 to 2018Enrolled100ConditionsHistologic Response (Tumor Necrosis Rate), Objective Response Rate for Neoadjuvant Chemotherapy, ORR, Progression-free Survival, PFS, Overall Survival, OS
3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. DNA Hydroxymethylation in Smoking-Associated Cancers.International journal of molecular sciences · 2022
    Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. ApcScientific reports · 2020
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Christopher G ChapmanSection of Gastroenterology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Christopher J MarianiSection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Feng WuSection of Gastroenterology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Katherine MeckelSection of Gastroenterology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Fatma ButunSection of Gastroenterology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Alice ChuangSection of Gastroenterology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Jozef MadzoSection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Marc B BissonnetteSection of Gastroenterology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
John H KwonSection of Gastroenterology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Lucy A GodleySection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
University of Chicago · US

Funding

Re-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2M
Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grant (Parent T32)T32HD007009 · NICHD · UNIVERSITY OF CHICAGO · PI NANCY B SCHWARTZ · 1985 to 2026
$13.0M
Research Training in Digestive Health, Diseases, and NutritionT32DK007074 · NIDDK · UNIVERSITY OF CHICAGO · PI EUGENE B CHANG · 1986 to 2026
$11.3M
Roles of EGFR and miR-143/miR-145 in Western diet-promoted colonic tumorigenesisR01CA164124 · NCI · UNIVERSITY OF CHICAGO · PI BISSONNETTE, BRUCE MARC · 2012 to 2016
$1.6M
NCATS NIH HHS UL1 TR000430NCI NIH HHS R01 CA164124NICHD NIH HHS T32 HD007009NIDDK NIH HHS T32 DK007074
6 · The paper itself

Abstract

The formation of differentiated cell types from pluripotent progenitors involves epigenetic regulation of gene expression. DNA hydroxymethylation results from the enzymatic oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) 5-mC dioxygenase enzymes. Previous work has mapped changes in 5-mC during differentiation of intestinal stem cells. However, whether or not 5-hmC regulates colonocyte differentiation is unknown. Here we show that 5-hmC regulates gene expression during colonocyte differentiation and controls gene expression in human colon cancers. Genome-wide profiling of 5-hmC during in vitro colonic differentiation demonstrated that 5-hmC is gained at highly expressed and induced genes and is associated with intestinal transcription factor binding sites, including those for HNF4A and CDX2. TET1 induction occurred during differentiation, and TET1 knockdown altered gene expression and inhibited barrier formation of colonocytes. We find that the 5-hmC distribution in primary human colonocytes parallels the distribution found in differentiated cells in vitro, and that gene-specific 5-hmC changes in human colon cancers are directly correlated with changes in gene expression. Our results support a model in which 5-hmC regulates differentiation of adult human intestine and 5-hmC alterations contribute to the disrupted gene expression in colon cancer.

Indexed as

5-MethylcytosineAdenocarcinomaBinding SitesCell DifferentiationCell Line, TumorColonColonic NeoplasmsCytosineGene Expression RegulationGene Expression Regulation, NeoplasticHumansMixed Function OxygenasesProto-Oncogene ProteinsTranscription Factors5-hydroxymethylcytosine5-MethylcytosineCytosineMixed Function OxygenasesProto-Oncogene ProteinsTET1 protein, humanTranscription Factors

Identifiers

PMID26631571
PMCPMC4668370
OpenAlexW2182886286

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Registered trials

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.