Geometric regulation of histone state directs melanoma reprogramming

Malignant melanoma displays a high degree of cellular plasticity during disease progression. Signals in the tumor microenvironment are believed to influence melanoma plasticity through changes in the epigenetic state to guide dynamic differentiation and de-differentiation. Here we uncover a relation...

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Veröffentlicht in:Communications biology 2020-07, Vol.3 (1), p.341-341, Article 341
Hauptverfasser: Lee, Junmin, Molley, Thomas G., Seward, Christopher H., Abdeen, Amr A., Zhang, Huimin, Wang, Xiaochun, Gandhi, Hetvi, Yang, Jia-Lin, Gaus, Katharina, Kilian, Kristopher A.
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container_issue 1
container_start_page 341
container_title Communications biology
container_volume 3
creator Lee, Junmin
Molley, Thomas G.
Seward, Christopher H.
Abdeen, Amr A.
Zhang, Huimin
Wang, Xiaochun
Gandhi, Hetvi
Yang, Jia-Lin
Gaus, Katharina
Kilian, Kristopher A.
description Malignant melanoma displays a high degree of cellular plasticity during disease progression. Signals in the tumor microenvironment are believed to influence melanoma plasticity through changes in the epigenetic state to guide dynamic differentiation and de-differentiation. Here we uncover a relationship between geometric features at perimeter regions of melanoma aggregates, and reprogramming to a stem cell-like state through histone marks H3K4Me2 and H3K9Ac. Using an in vitro tumor microengineering approach, we find spatial enrichment of these histone modifications with concurrent expression of stemness markers. The epigenetic modifier PRDM14 overlaps with H3K9Ac and shows elevated expression in cells along regions of perimeter curvature. siRNA knockdown of PRDM14 abolishes the MIC phenotype suggesting a role in regulating melanoma heterogeneity. Our results suggest mechanotransduction at the periphery of melanoma aggregates may orchestrate the activity of epigenetic modifiers to regulate histone state, cellular plasticity, and tumorigenicity. Junmin Lee et al. study the role of geometric features at the perimeter regions of melanoma aggregates in programming stem cell-like state through histone marks. They use a tumor microengineering approach in vitro and report a spatial enrichment of histone modifications with stemness markers. Their work uncovers a mechanotransduction signaling that regulates epigenetic modifiers to regulate tumorigenicity.
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subjects 13/100
13/106
13/107
45/15
631/532
631/57
631/67
692/699
Biology
Biomedical and Life Sciences
Epigenetics
Life Sciences
Mechanotransduction
Melanoma
Phenotypes
Plasticity
siRNA
Skin cancer
Stem cells
Tumorigenicity
title Geometric regulation of histone state directs melanoma reprogramming
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