Evidence map›Paper›PMID 36511816›Full record

ArticleCancer science2023

HNF1B-driven three-dimensional chromatin structure for molecular classification in pancreatic cancers.

Hiroyuki Kato, Keisuke Tateishi, Dosuke Iwadate, Keisuke Yamamoto, Hiroaki Fujiwara, Takuma Nakatsuka, Yotaro Kudo, Yoku Hayakawa, Hideaki Ijichi, Motoyuki Otsuka and 8 more

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

Article in Cancer science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 35% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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

18 authors at 5 institutions in 1 country.

Hiroyuki KatoDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0003-0655-1519
Keisuke TateishiDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0002-9837-0856
Dosuke IwadateDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Keisuke YamamotoDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0002-6323-9540
Hiroaki FujiwaraDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Takuma NakatsukaDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yotaro KudoDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0003-1869-2810
Yoku HayakawaDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0002-3988-2499
Hideaki IjichiDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Motoyuki OtsukaDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Takahiro KishikawaDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Ryota TakahashiDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Koji MiyabayashiDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yousuke NakaiDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yoshihiro HirataDivision of Advanced Genome Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Atsushi ToyodaComparative Genomics Laboratory, National Institute of Genetics, Shizuoka, Japan.
Shinichi MorishitaDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
Mitsuhiro FujishiroDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
The University of Tokyo · JPNational Institute of Genetics · JPSt. Marianna University School of Medicine · JPThe Institute of Medical Science, Asahi Life Foundation · JPUniversity of Tokyo Hospital · JP

Funding

Astellas Foundation for Research on Metabolic DisordersInternational Joint Usage/Research Center, the Institute of Medical Science, the University of TokyoJapan Society for the Promotion of Science 16H06279 (PAGS)Japan Society for the Promotion of Science 19K08435Japan Society for the Promotion of Science 21K15966Japan Society for the Promotion of Science 21K20828Japan Society for the Promotion of Science 22H02898Japan Society for the Promotion of Science 22H03053Life Science Foundation of JapanMSD Life Science Foundation, Public Interest Incorporated FoundationPrincess Takamatsu Cancer Research FundTakeda Science FoundationThe International Joint Usage/Research Center, Institute of Medical Science, the University of TokyoTokyo Society of Medical ScienceUehara Memorial FoundationYasuda Medical FoundationYasuda Memorial Medical Foundation
6 · The paper itself

Abstract

The molecular subtypes of pancreatic cancer (PC), either classical/progenitor-like or basal/squamous-like, are currently a major topic of research because of their direct association with clinical outcomes. Some transcription factors (TFs) have been reported to be associated with these subtypes. However, the mechanisms by which these molecular signatures of PCs are established remain unknown. Epigenetic regulatory processes, supported by dynamic changes in the chromatin structure, are essential for transcriptional profiles. Previously, we reported the importance of open chromatin profiles in the biological features and transcriptional status of PCs. Here, we aimed to analyze the relationships between three-dimensional (3D) genome structures and the molecular subtypes of human PCs using Hi-C analysis. We observed a correlation of the specific elements of 3D genome modules, including compartments, topologically associating domains, and enhancer-promoter loops, with the expression of related genes. We focused on HNF1B, a TF that is implicated in the progenitor subtype. Forced expression of HNF1B in squamous-type PC organoids induced the upregulation and downregulation of genes associated with progenitor and squamous subtypes, respectively. Long-range genomic interactions induced by HNF1B were accompanied by compartment modulation and H3K27ac redistribution. We also found that these HNF1B-induced changes in subtype-related gene expression required an intrinsically disordered region, suggesting a possible involvement of phase separation in compartment modulation. Thus, mapping of 3D structural changes induced by TFs, such as HNF1B, may become a useful resource for further understanding the molecular features of PCs.

Indexed as

Carcinoma, Squamous CellGenomeChromatinEpigenesis, GeneticHepatocyte Nuclear Factor 1-betaHumansTranscription FactorsChromatinHepatocyte Nuclear Factor 1-betaHNF1B protein, humanTranscription FactorsHi-CHNF1Bintrinsically disordered regionpancreatic cancerpatient-derived organoid

Identifiers

PMID36511816
PMCPMC10067390
OpenAlexW4311243451

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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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.