Related Experiment Video

Updated: May 29, 2025

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

27.2K

The PRC2.1 subcomplex opposes G1 progression through regulation of CCND1 and CCND2

Adam D Longhurst1,2, Kyle Wang3,4, Harsha Garadi Suresh3

  • 1University of California, San Francisco, San Francisco, United States.

Elife
|February 4, 2025
PubMed

Insights

Polycomb Repressor Complex 2 (PRC2.1) protein MTF2 is crucial for cell cycle progression. Loss of MTF2 confers resistance to CDK4/6 inhibitors by upregulating CCND1 and CCND2, impacting cancer cell proliferation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Epigenetics

Background:

  • Cell cycle progression, particularly the G1 phase, is tightly regulated.
  • Identifying novel regulators of cell cycle control is essential for understanding cellular division and developing targeted therapies.

Purpose of the Study:

  • To discover novel cellular networks regulating cell cycle progression using a chemogenetic approach.
  • To investigate the role of Polycomb Repressor Complex 2 (PRC2) components in cell cycle regulation and response to G1/S transition inhibitors.

Main Methods:

  • Chemogenetic screening to identify gene clusters affecting sensitivity to G1/S inhibitors.
  • Mutation analysis of Polycomb Repressor Complex 2 (PRC2) components, including MTF2 and JARID2.
  • Assays to assess H3K27me3 deposition and gene expression of CCND1 and CCND2.

Main Results:

  • Mutation of PRC2 components rescued proliferation inhibition by the CDK4/6 inhibitor palbociclib.
  • Loss of PRC2.1 component MTF2, but not PRC2.2 component JARID2, conferred resistance to palbociclib.
  • MTF2 is essential for H3K27me3 deposition at CpG islands, including promoters of CCND1 and CCND2, and its loss upregulated these cyclins.

Conclusions:

  • PRC2.1, specifically MTF2, antagonizes G1 phase progression in various cell lineages.
  • MTF2's role in regulating CCND1/CCND2 expression is critical for sensitivity to CDK4/6 inhibition.
  • These findings highlight PRC2.1 as a potential therapeutic target in cancers driven by CDK4/6 pathway dysregulation.
Keywords:
D-type cyclinscell biologycell cyclegeneticsgenomicshumanmolecular biologypalbociclib

More Related Videos

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

18.5K
Analysis of Cell Cycle Position in Mammalian Cells12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

60.1K

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.
35.1K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.6K
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.
5.3K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.8K
The Cell Cycle Control System01:28

The Cell Cycle Control System

The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
2.6K
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
3.6K