Evidence map›Paper›PMID 31097695›Full record

ArticleNature communications2019

Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers.

Mizuo Ando, Yuki Saito, Guorong Xu, Nam Q Bui, Kate Medetgul-Ernar, Minya Pu, Kathleen Fisch, Shuling Ren, Akihiro Sakai, Takahito Fukusumi and 15 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

73 citing papers in PubMed, 108 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Epigenetic alterations in Myeloid Malignancies.Advances in experimental medicine and biology · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 6 institutions in 3 countries.

Mizuo AndoMoores Cancer Center, University of California San Diego, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0002-0754-2545
Yuki SaitoMoores Cancer Center, University of California San Diego, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA.
Guorong XuDepartment of Medicine, Center for Computational Biology and Bioinformatics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Nam Q BuiDepartment of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0001-6896-4349
Kate Medetgul-ErnarMoores Cancer Center, University of California San Diego, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA.
Minya PuMoores Cancer Center, University of California San Diego, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA.
Kathleen FischDepartment of Medicine, Center for Computational Biology and Bioinformatics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0002-0117-7444
Shuling RenMoores Cancer Center, University of California San Diego, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA.
Akihiro SakaiMoores Cancer Center, University of California San Diego, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA.
Takahito FukusumiMoores Cancer Center, University of California San Diego, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA.
Chao LiuMoores Cancer Center, University of California San Diego, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA.
Sunny HaftMoores Cancer Center, University of California San Diego, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA.
John PangMoores Cancer Center, University of California San Diego, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA.
Adam MarkDepartment of Medicine, Center for Computational Biology and Bioinformatics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Daria A GaykalovaDepartment of Otolaryngology - Head and Neck Surgery, Johns Hopkins University School of Medicine, 601 N Caroline St, Baltimore, MD, 21287, USA.
Theresa GuoDepartment of Otolaryngology - Head and Neck Surgery, Johns Hopkins University School of Medicine, 601 N Caroline St, Baltimore, MD, 21287, USA.
Alexander V FavorovDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 401 N Broadway, Baltimore, MD, 21231, USA.ORCID http://orcid.org/0000-0003-2595-1091
Srinivasan YegnasubramanianDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 401 N Broadway, Baltimore, MD, 21231, USA.
Elana J FertigDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 401 N Broadway, Baltimore, MD, 21231, USA.
Patrick HaDepartment of Otolaryngology - Head and Neck Surgery, University of California San Francisco, 2380 Sutter St, San Francisco, CA, 94115, USA.ORCID http://orcid.org/0000-0003-0306-6147
Pablo TamayoMoores Cancer Center, University of California San Diego, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0002-9360-4668
Tatsuya YamasobaDepartment of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.ORCID http://orcid.org/0000-0003-3608-0973
Trey IdekerDepartment of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Karen MesserMoores Cancer Center, University of California San Diego, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA.
Joseph A CalifanoMoores Cancer Center, University of California San Diego, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA. jcalifano@ucsd.edu.
University of California San Diego · USJohns Hopkins University · USPalo Alto University · USThe University of Tokyo · JPUC San Diego Health System · USUniversity of California, San Francisco · US

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
TUMOR SUPPRESOR GENE PROMOTER HYPERMETHYLATION FOR DETECTION OF HEAD AND NECKP50DE019032 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI SIDRANSKY, DAVID · 2007 to 2016
$27.1M
A Rational Systematic Approach to Find Combinations of Pharmacologic and Immune Therapies that Target Identifiable Oncogenic StatesU01CA217885 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COHEN, EZRA, KAUFMAN, DAN S. · 2017 to 2021
$5.1M
Next-generation Functional Genetic Screening of Un-screenable TraitsR01HG009285 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MALI, PRASHANT, TAMAYO, PABLO · 2017 to 2020
$4.2M
Supporting and evolving Gene Set Enrichment Analysis and the Molecular Signatures Database for cancer researchU24CA220341 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MESIROV, JILL P., TAMAYO, PABLO · 2018 to 2022
$3.4M
GenePattern Notebooks for Cancer ResearchU24CA194107 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MESIROV, JILL P. · 2015 to 2019
$2.8M
Epigenetic Biomarker Discovery in HPV Related HNSCCR01DE023347 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CALIFANO, JOSEPH A · 2013 to 2017
$1.9M
Systematic mapping of genetic vulnerabilities in head and neck cancerR01CA222826 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MALI, PRASHANT · 2018 to 2022
$1.8M
Detection/Dysplastic Epithelium/Gastrointestinal TractR33CA094304 · NCI · UNIVERSITY HOSPITALS OF CLEVELAND · PI SIVAK, MICHAEL V · 2002 to 2004
$1.5M
Dissecting the interplay of gene regulatory networks and cellular niche on cell fate determinationR01GM123313 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MALI, PRASHANT · 2018 to 2021
$1.2M
NCATS NIH HHS UL1 TR001442NCI NIH HHS R01 CA222826NCI NIH HHS R33 CA094304NCI NIH HHS U01 CA217885NCI NIH HHS U24 CA194107NCI NIH HHS U24 CA220341NHGRI NIH HHS R01 HG009285NIDCR NIH HHS P50 DE019032NIDCR NIH HHS R01 DE023347NIGMS NIH HHS R01 GM123313
6 · The paper itself

Abstract

Although promoter-associated CpG islands have been established as targets of DNA methylation changes in cancer, previous studies suggest that epigenetic dysregulation outside the promoter region may be more closely associated with transcriptional changes. Here we examine DNA methylation, chromatin marks, and transcriptional alterations to define the relationship between transcriptional modulation and spatial changes in chromatin structure. Using human papillomavirus-related oropharyngeal carcinoma as a model, we show aberrant enrichment of repressive H3K9me3 at the transcriptional start site (TSS) with methylation-associated, tumor-specific gene silencing. Further analysis identifies a hypermethylated subtype which shows a functional convergence on MYC targets and association with CREBBP/EP300 mutation. The tumor-specific shift to transcriptional repression associated with DNA methylation at TSSs was confirmed in multiple tumor types. Our data may show a common underlying epigenetic dysregulation in cancer associated with broad enrichment of repressive chromatin marks and aberrant DNA hypermethylation at TSSs in combination with MYC network activation.

Indexed as

Gene Expression Regulation, NeoplasticTranscription Initiation SiteCell Line, TumorChromatinCREB-Binding ProteinDatasets as TopicDNA MethylationE1A-Associated p300 ProteinGene SilencingHistonesHumansMutationNeoplasmsProto-Oncogene Proteins c-mycSignal TransductionChromatinCREB-Binding ProteinCREBBP protein, humanE1A-Associated p300 ProteinEP300 protein, humanHistonesMYC protein, humanProto-Oncogene Proteins c-myc

Identifiers

PMID31097695
PMCPMC6522544
OpenAlexW2946296908

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.