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Review
. 2022 Jun:74:101901.
doi: 10.1016/j.gde.2022.101901. Epub 2022 Apr 12.

Oncogenic fusion proteins and their role in three-dimensional chromatin structure, phase separation, and cancer

Ivana Y Quiroga  1 , Jeong Hyun Ahn  2 , Gang Greg Wang  3 , Douglas Phanstiel  4
Affiliations
Review

Oncogenic fusion proteins and their role in three-dimensional chromatin structure, phase separation, and cancer

Ivana Y Quiroga et al. Curr Opin Genet Dev. 2022 Jun.

Abstract

Three-dimensional (3D) chromatin structure plays a critical role in development, gene regulation, and cellular identity. Alterations to this structure can have profound effects on cellular phenotypes and have been associated with a variety of diseases including multiple types of cancer. One of several forces that help shape 3D chromatin structure is liquid-liquid phase separation, a form of self-association between biomolecules that can sequester regions of chromatin into subnuclear droplets or even membraneless organelles like nucleoli. This review focuses on a class of oncogenic fusion proteins that appear to exert their oncogenic function via phase-separation-driven alterations to 3D chromatin structure. Here, we review what is known about the mechanisms by which these oncogenic fusion proteins phase separate in the nucleus and their role in shaping the 3D chromatin structure. We discuss the potential for this phenomenon to be a more widespread mechanism of oncogenesis.

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Conflict of interest statement

Declarations of interest

none

Figures

Figure 1.
Figure 1.. IDR/chromatin-associating fusion proteins in cancer.
A. The proposed mechanism of action of IDR/chromatin-associating fusion proteins in cancer. Fusion proteins bind chromatin at enhancers and gene promoters and recruit bound loci into phase separation dependent condensates activating oncogenic transcriptional profiles. B. A list of IDR/DNA-binding fusion proteins frequently found in cancer that have been described to phase separate in the nucleus. *In vitro/in vivo assays for coalescence, fusion/fission, concentration dependency. FRAP: Fluorescence recovery after photobleaching.
See this image and copyright information in PMC

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