한빛사 논문
Hyo-Min Kim 1, Byunghee Kang 1, Sohyun Park 1, Hyorim Park 1, Chan Johng Kim 1, Hyeonji Lee 1, Mijoung Yoo 1, Mi-Na Kweon 2, Sin-Hyeog Im 1,3,4, Tae Il Kim 5 and Tae-Young Roh 6,7,*
1Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea,
2Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea,
3Institute of Convergence Science, Yonsei University, Seoul 03722, Republic of Korea,
4ImmunoBiome, Inc., Pohang 37666, Republic of Korea,
5Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea,
6Department of Life Sciences, Ewha Womans University, Seoul 03760, Republic of Korea
7Sysgenlab Inc., Pohang 37673, Republic of Korea
To whom correspondence should be addressed. : Tae-Young Roh
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.
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