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Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...

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Related Experiment Video

Updated: May 11, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

BRCA1 is a negative modulator of the PRC2 complex.

Lan Wang1, Xianzhuo Zeng, Shuai Chen

  • 1Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA.

The EMBO Journal
|April 30, 2013
PubMed
Summary

The tumor suppressor BRCA1 negatively regulates Polycomb Repressive Complex 2 (PRC2) by interacting with EZH2. Loss of BRCA1 impairs stem cell differentiation and promotes aggressive breast cancer via PRC2.

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Last Updated: May 11, 2026

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Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
08:53

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1

Published on: February 17, 2011

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cancer Biology

Background:

  • Polycomb-repressive complex 2 (PRC2) epigenetically regulates gene expression by catalyzing histone H3 lysine 27 trimethylation (H3K27me3).
  • PRC2 is crucial for maintaining stem cell pluripotency and suppressing differentiation.
  • Aberrant PRC2 activity is implicated in various cancers, including breast cancer.

Purpose of the Study:

  • To investigate the interaction between tumor suppressor BRCA1 and PRC2 component EZH2.
  • To elucidate the role of BRCA1 in modulating PRC2 function in embryonic stem cells and breast cancer.

Main Methods:

  • Co-immunoprecipitation assays to detect BRCA1-EZH2 interaction.
  • RNA immunoprecipitation followed by sequencing (RIP-seq) to assess EZH2 binding to HOTAIR ncRNA.
  • Chromatin immunoprecipitation (ChIP) to quantify H3K27me3 levels.
  • Cell differentiation assays in mouse embryonic stem cells.
  • Cell migration and invasion assays in human breast cancer cells.

Main Results:

  • BRCA1 directly interacts with EZH2, inhibiting its binding to HOTAIR ncRNA.
  • BRCA1 deficiency leads to genome-wide EZH2 re-targeting and increased H3K27me3 levels at PRC2 target loci.
  • Loss of BRCA1 impairs mouse embryonic stem cell differentiation and enhances human breast cancer cell migration and invasion.
  • These effects are dependent on EZH2 activity.

Conclusions:

  • BRCA1 acts as a critical negative regulator of PRC2 activity.
  • Loss of BRCA1 function disrupts stem cell homeostasis and promotes an aggressive breast cancer phenotype through aberrant PRC2 modulation.