FOXA2 controls the cis-regulatory networks of pancreatic cancer cells in a differentiation grade-specific manner.
Carcinoma, Pancreatic Ductal
/ genetics
Cell Differentiation
Cell Movement
Cell Proliferation
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Hepatocyte Nuclear Factor 1-beta
/ genetics
Hepatocyte Nuclear Factor 3-alpha
/ genetics
Hepatocyte Nuclear Factor 3-beta
/ genetics
Homeodomain Proteins
/ genetics
Humans
Neoplasm Grading
Pancreatic Neoplasms
/ genetics
Regulatory Elements, Transcriptional
Tumor Cells, Cultured
FOXA2
differentiation
pancreatic cancer
transcription
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
15 10 2019
15 10 2019
Historique:
received:
02
04
2019
revised:
09
08
2019
accepted:
12
08
2019
pubmed:
19
9
2019
medline:
7
1
2020
entrez:
19
9
2019
Statut:
ppublish
Résumé
Differentiation of normal and tumor cells is controlled by regulatory networks enforced by lineage-determining transcription factors (TFs). Among them, TFs such as FOXA1/2 bind naïve chromatin and induce its accessibility, thus establishing new gene regulatory networks. Pancreatic ductal adenocarcinoma (PDAC) is characterized by the coexistence of well- and poorly differentiated cells at all stages of disease. How the transcriptional networks determining such massive cellular heterogeneity are established remains to be determined. We found that FOXA2, a TF controlling pancreas specification, broadly contributed to the cis-regulatory networks of PDACs. Despite being expressed in both well- and poorly differentiated PDAC cells, FOXA2 displayed extensively different genomic distributions and controlled distinct gene expression programs. Grade-specific functions of FOXA2 depended on its partnership with TFs whose expression varied depending on the differentiation grade. These data suggest that FOXA2 contributes to the regulatory networks of heterogeneous PDAC cells via interactions with alternative partner TFs.
Identifiants
pubmed: 31531882
doi: 10.15252/embj.2019102161
pmc: PMC6792020
doi:
Substances chimiques
FOXA1 protein, human
0
FOXA2 protein, human
0
HNF1B protein, human
0
HOXB8 protein, human
0
Hepatocyte Nuclear Factor 3-alpha
0
Homeodomain Proteins
0
Hepatocyte Nuclear Factor 3-beta
135845-92-0
Hepatocyte Nuclear Factor 1-beta
138674-15-4
Banques de données
GEO
['GSE120017']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e102161Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro (AIRC)
ID : 20251
Pays : International
Organisme : Ministero della Salute (Ministry of Health, Italy)
ID : GR-2016-02361721
Pays : International
Organisme : Umberto Veronesi Foundation (FUV)
Pays : International
Informations de copyright
© 2019 The Authors.
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