Related Experiment Video

Updated: Jul 6, 2026

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

SWI/SNF mediates polycomb eviction and epigenetic reprogramming of the INK4b-ARF-INK4a locus

Sima Kheradmand Kia1, Marcin M Gorski, Stavros Giannakopoulos

  • 1Department of Biochemistry, Center for Biomedical Genetics, Erasmus University Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.

Molecular and Cellular Biology
|March 12, 2008
PubMed

Insights

Malignant rhabdoid tumors (MRTs) involve silencing of tumor suppressors. Restoring SWI/SNF activity in MRT cells reactivates silenced genes by removing Polycomb silencers and altering chromatin states.

Area of Science:

  • Cancer Biology
  • Epigenetics
  • Chromatin Remodeling

Background:

  • Malignant rhabdoid tumors (MRTs) are aggressive cancers characterized by the loss of the hSNF5 subunit of the SWI/SNF chromatin-remodeling complex.
  • The INK4b-ARF-INK4a tumor suppressor locus is stably silenced in MRTs and other human cancers.
  • Previous work showed hSNF5 is crucial for p16(INK4a) induction, mitotic checkpoint activation, and senescence in MRT cells.

Purpose of the Study:

  • To investigate the interplay between Polycomb group (PcG) silencing and SWI/SNF activation in epigenetic control of the INK4b-ARF-INK4a locus in MRT cells.
  • To understand how SWI/SNF complex activity influences chromatin states and gene expression in the context of MRTs.

Main Methods:

  • Reexpression of hSNF5 in MRT cells.
  • Analysis of SWI/SNF recruitment and chromatin remodeling.
  • Assessment of Polycomb group (PcG) complex eviction (PRC1, PRC2).
  • Evaluation of histone modifications and DNA methylation changes.

Main Results:

  • hSNF5 reexpression reactivated p15(INK4b) and p16(INK4a) but not p14(ARF) in MRT cells, dependent on the BRG1 subunit.
  • SWI/SNF mediated the eviction of PRC1 and PRC2 PcG silencers, leading to extensive chromatin reprogramming.
  • Recruitment of MLL1 and replacement of repressive histone marks with active ones were observed.
  • Loss of PcG complexes correlated with dissociation of DNMT3B and reduced DNA methylation.

Conclusions:

  • SWI/SNF action modulates chromatin states by displacing PcG complexes and altering epigenetic marks.
  • The findings highlight the dynamic interplay of diverse chromatin modifications in cancer gene control.
  • SWI/SNF-mediated chromatin remodeling is a key mechanism in regulating the INK4b-ARF-INK4a locus in MRTs.

More Related Videos

Identification of Modified Histones as Binding Substrates of Human Spindlin Family Member 4 (SPIN4) by Peptide Arrays and Native Nucleosome Pulldown09:34

Identification of Modified Histones as Binding Substrates of Human Spindlin Family Member 4 (SPIN4) by Peptide Arrays and Native Nucleosome Pulldown

Published on: March 27, 2026

Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome11:15

Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome

Published on: March 2, 2018

Related Concept Videos

Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
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...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-Inactivation01:58

X-Inactivation

The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.