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Related Concept Videos

Nucleosome Remodeling02:54

Nucleosome Remodeling

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Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
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Spreading of Chromatin Modifications02:25

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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
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The writer...
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Heterochromatin02:38

Heterochromatin

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The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
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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...
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Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

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Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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Updated: May 10, 2025

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

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The SWI/SNF PBAF complex facilitates REST occupancy at repressive chromatin.

Elena Grossi1, Christie B Nguyen2, Saul Carcamo3

  • 1Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Molecular Cell
|April 19, 2025
PubMed
Summary
This summary is machine-generated.

The polybromo-associated BAF (PBAF) complex, specifically its ARID2 component, plays a crucial role in regulating gene expression in melanoma. Loss of ARID2 disrupts the silencing of neuronal genes, impacting melanoma progression and brain metastasis.

Keywords:
ARID2PBAFPolycombRESTSWI/SNFchromatin remodelersmelanomatranscription factors

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Area of Science:

  • Molecular Biology
  • Cancer Genomics
  • Epigenetics

Background:

  • Switch/sucrose non-fermentable (SWI/SNF) chromatin remodelers are essential for cellular function.
  • Mutations in SWI/SNF subunits, like ARID2 in the polybromo-associated BAF (PBAF) complex, are implicated in various cancers, including melanoma.

Purpose of the Study:

  • To investigate the specific role of the PBAF complex in melanocytes and melanoma.
  • To elucidate the function of ARID2 within the PBAF complex in regulating chromatin accessibility and gene expression.

Main Methods:

  • Epigenomic profiling of SWI/SNF complexes and chromatin states.
  • Time-resolved analyses of ATPase inhibition sensitivity.
  • Investigation of REST transcription factor binding in wild-type and ARID2-deficient cells.

Main Results:

  • PBAF regions exhibit distinct sensitivity to ATPase inhibition compared to BAF sites.
  • PBAF selectively targets Polycomb-repressed chromatin enriched for the RE1 silencing transcription factor (REST).
  • ARID2 loss impairs REST binding, leading to the upregulation of synaptic transcripts, a signature found in ARID2-mutant melanoma and brain metastases.

Conclusions:

  • The PBAF complex uniquely facilitates transcription factor access to repressed chromatin.
  • ARID2's role in PBAF is critical for repressing neuronal gene expression in melanoma.
  • This mechanism has significant implications for understanding melanoma progression and metastasis.