# Noncanonical association of EZH2 with E2F1 promotes tumor proliferation through chromatin remodeling

## TL;DR

EZH2 helps aggressive breast cancer grow by working with E2F1 to change how DNA is packaged, even without its usual role.

## Contribution

EZH2's noncanonical role in chromatin remodeling through E2F1 interaction in TNBC is revealed.

## Key findings

- EZH2 binds to E2F1 to modulate chromatin accessibility independently of PRC2.
- EZH2-E2F1 interaction promotes tumor proliferation and inhibits apoptosis in TNBC.
- EZH2's function in TNBC is chromatin context-dependent and distinct from its canonical role.

## Abstract

Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2 (PRC2), which mediates transcriptional repression through histone H3 lysine 27 trimethylation (H3K27me3), is highly expressed in aggressive triple-negative breast cancer (TNBC). However, despite the elevated EZH2 expression, H3K27me3 levels remain unexpectedly low, suggesting a potential noncanonical role for EZH2 in TNBC. Here we demonstrate that EZH2 directly binds to the transcription factor E2F1, and this interaction is critical for modulating chromatin accessibility by disrupting H3K27me3 deposition. This noncanonical function of EZH2, which operates independently of its methyltransferase activity, is linked to enhanced tumor cell proliferation and inhibition of apoptosis. Our findings reveal that EZH2 functions in a chromatin context-dependent manner by cooperating with E2F1 in TNBC, highlighting that the EZH2–E2F1 interaction, independent of PRC2, plays a key role in remodeling chromatin structure and facilitating TNBC proliferation.

Breast cancer is a leading cancer type in women, with triple-negative breast cancer (TNBC) being particularly aggressive and hard to treat. This study addresses the role of a protein called EZH2 in TNBC, which is known for its involvement in gene regulation. Here researchers explored how EZH2 functions beyond its usual role in a complex called PRC2. The study used various laboratory techniques to investigate how EZH2 interacts with another protein, E2F1, in TNBC cells. They found that EZH2 and E2F1 work together to regulate the cell cycle and prevent cell death, which helps cancer cells grow. The results showed that EZH2 has a unique function in TNBC that does not rely on its typical role in PRC2. This discovery suggests new ways to target TNBC by disrupting the interaction between EZH2 and E2F1.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.