Related Experiment Video

Updated: Oct 7, 2025

CRISPR-Mediated Reorganization of Chromatin Loop Structure
09:20

CRISPR-Mediated Reorganization of Chromatin Loop Structure

Published on: September 14, 2018

12.7K

BCOR and BCORL1 Mutations Drive Epigenetic Reprogramming and Oncogenic Signaling by Unlinking PRC1.1 from Target

Eva J Schaefer1, Helen C Wang1, Hannah Q Karp1

  • 1Department of Medical Oncology, Division of Hematologic Neoplasia, Dana-Farber Cancer Institute, Boston, Massachusetts.

Blood Cancer Discovery
|January 11, 2022
PubMed

Insights

Mutations in BCOR and BCORL1 disrupt Polycomb Repressive Complex 1.1 (PRC1.1) function in leukemia, causing epigenetic changes, activating oncogenic signals, and leading to treatment resistance.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Polycomb repressive complexes (PRCs) are crucial epigenetic regulators frequently altered in cancer.
  • The specific role of Polycomb Repressive Complex 1 (PRC1) in oncogenesis and therapy resistance remains less understood compared to PRC2.
  • Recurrent mutations in BCOR and BCORL1 subunits are observed in certain leukemias.

Purpose of the Study:

  • To investigate the functional consequences of BCOR and BCORL1 mutations in leukemia.
  • To elucidate the role of the noncanonical PRC1.1 complex in cancer development and treatment resistance.
  • To identify potential therapeutic strategies for PRC1.1-mutated cancers.

Main Methods:

  • Analysis of PRC1.1 complex assembly and function in leukemia models.
  • Chromatin immunoprecipitation and sequencing to assess PRC1.1 localization and target genes.
  • Transcriptomic analysis to identify dysregulated signaling pathways.
  • Assessment of treatment resistance and sensitivity in cellular and patient-derived samples.

Main Results:

  • BCOR/BCORL1 mutations disrupt PRC1.1 assembly, unlinking its enzymatic core from chromatin-targeting components.
  • Mutated PRC1.1 localizes to chromatin but loses repressive activity, causing epigenetic reprogramming.
  • Aberrant activation of specific target genes drives oncogenic signaling and confers treatment resistance.
  • PRC1.1 target gene activation sensitizes cells to targeted kinase inhibition.

Conclusions:

  • BCOR/BCORL1 mutations impair PRC1.1 tumor-suppressive activity through a novel epigenetic mechanism.
  • Dysfunctional PRC1.1 leads to epigenetic reprogramming and activation of oncogenic pathways in leukemia.
  • Targeting PRC1.1-driven pathways represents a promising therapeutic strategy for affected cancers.

More Related Videos

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells10:26

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells

Published on: January 20, 2019

12.5K
Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells09:24

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

Published on: August 12, 2015

9.3K

Related Concept Videos

Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.2K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.5K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.2K
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...
4.7K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.7K