FOXA2 controls the cis-regulatory networks of pancreatic cancer cells in a differentiation grade-specific manner.
EMBO J
; 38(20): e102161, 2019 10 15.
Article
en En
| MEDLINE
| ID: mdl-31531882
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
/
2_ODS3
Problema de salud:
1_doencas_nao_transmissiveis
/
2_muertes_prematuras_enfermedades_notrasmisibles
Asunto principal:
Neoplasias Pancreáticas
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Regulación Neoplásica de la Expresión Génica
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Diferenciación Celular
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Proteínas de Homeodominio
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Factor Nuclear 1-beta del Hepatocito
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Factor Nuclear 3-beta del Hepatocito
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Elementos Reguladores de la Transcripción
Límite:
Humans
Idioma:
En
Revista:
EMBO J
Año:
2019
Tipo del documento:
Article
País de afiliación:
Italia