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Updated: Sep 27, 2025

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
Oncogenic fusion proteins and their role in three-dimensional chromatin structure, phase separation, and cancer
Ivana Y Quiroga1, Jeong Hyun Ahn2, Gang Greg Wang2
1Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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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