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HNF1B‐driven three‐dimensional chromatin structure for molecular classification in pancreatic cancers
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. How...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067390/ https://www.ncbi.nlm.nih.gov/pubmed/36511816 http://dx.doi.org/10.1111/cas.15690 |
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author | Kato, Hiroyuki Tateishi, Keisuke Iwadate, Dosuke Yamamoto, Keisuke Fujiwara, Hiroaki Nakatsuka, Takuma Kudo, Yotaro Hayakawa, Yoku Ijichi, Hideaki Otsuka, Motoyuki Kishikawa, Takahiro Takahashi, Ryota Miyabayashi, Koji Nakai, Yousuke Hirata, Yoshihiro Toyoda, Atsushi Morishita, Shinichi Fujishiro, Mitsuhiro |
author_facet | Kato, Hiroyuki Tateishi, Keisuke Iwadate, Dosuke Yamamoto, Keisuke Fujiwara, Hiroaki Nakatsuka, Takuma Kudo, Yotaro Hayakawa, Yoku Ijichi, Hideaki Otsuka, Motoyuki Kishikawa, Takahiro Takahashi, Ryota Miyabayashi, Koji Nakai, Yousuke Hirata, Yoshihiro Toyoda, Atsushi Morishita, Shinichi Fujishiro, Mitsuhiro |
author_sort | Kato, Hiroyuki |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10067390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100673902023-04-04 HNF1B‐driven three‐dimensional chromatin structure for molecular classification in pancreatic cancers Kato, Hiroyuki Tateishi, Keisuke Iwadate, Dosuke Yamamoto, Keisuke Fujiwara, Hiroaki Nakatsuka, Takuma Kudo, Yotaro Hayakawa, Yoku Ijichi, Hideaki Otsuka, Motoyuki Kishikawa, Takahiro Takahashi, Ryota Miyabayashi, Koji Nakai, Yousuke Hirata, Yoshihiro Toyoda, Atsushi Morishita, Shinichi Fujishiro, Mitsuhiro Cancer Sci ORIGINAL ARTICLES 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. John Wiley and Sons Inc. 2022-12-25 /pmc/articles/PMC10067390/ /pubmed/36511816 http://dx.doi.org/10.1111/cas.15690 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | ORIGINAL ARTICLES Kato, Hiroyuki Tateishi, Keisuke Iwadate, Dosuke Yamamoto, Keisuke Fujiwara, Hiroaki Nakatsuka, Takuma Kudo, Yotaro Hayakawa, Yoku Ijichi, Hideaki Otsuka, Motoyuki Kishikawa, Takahiro Takahashi, Ryota Miyabayashi, Koji Nakai, Yousuke Hirata, Yoshihiro Toyoda, Atsushi Morishita, Shinichi Fujishiro, Mitsuhiro HNF1B‐driven three‐dimensional chromatin structure for molecular classification in pancreatic cancers |
title | HNF1B‐driven three‐dimensional chromatin structure for molecular classification in pancreatic cancers |
title_full | HNF1B‐driven three‐dimensional chromatin structure for molecular classification in pancreatic cancers |
title_fullStr | HNF1B‐driven three‐dimensional chromatin structure for molecular classification in pancreatic cancers |
title_full_unstemmed | HNF1B‐driven three‐dimensional chromatin structure for molecular classification in pancreatic cancers |
title_short | HNF1B‐driven three‐dimensional chromatin structure for molecular classification in pancreatic cancers |
title_sort | hnf1b‐driven three‐dimensional chromatin structure for molecular classification in pancreatic cancers |
topic | ORIGINAL ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067390/ https://www.ncbi.nlm.nih.gov/pubmed/36511816 http://dx.doi.org/10.1111/cas.15690 |
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