Forkhead box protein D2 suppresses colorectal cancer by reprogramming enhancer interactions.
Nucleic Acids Res
; 51(12): 6143-6155, 2023 07 07.
Article
en En
| MEDLINE
| ID: mdl-37158258
ABSTRACT
Somatic stem cells contribute to normal tissue homeostasis, and their epigenomic features play an important role in regulating tissue identities or developing disease states. Enhancers are one of the key players controlling chromatin context-specific gene expression in a spatial and temporal manner while maintaining tissue homeostasis, and their dysregulation leads to tumorigenesis. Here, epigenomic and transcriptomic analyses reveal that forkhead box protein D2 (FOXD2) is a hub for the gene regulatory network exclusive to large intestinal stem cells, and its overexpression plays a significant role in colon cancer regression. FOXD2 is positioned at the closed chromatin and facilitates mixed-lineage leukemia protein-4 (MLL4/KMT2D) binding to deposit H3K4 monomethylation. De novo FOXD2-mediated chromatin interactions rewire the regulation of p53-responsive genes and induction of apoptosis. Taken together, our findings illustrate the novel mechanistic details of FOXD2 in suppressing colorectal cancer growth and suggest its function as a chromatin-tuning factor and a potential therapeutic target for colorectal cancer.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Histonas
/
Neoplasias Colorrectales
Límite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2023
Tipo del documento:
Article