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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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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...
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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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SWI/SNF-dependent genes are defined by their chromatin landscape.

Laura Basurto-Cayuela1, José A Guerrero-Martínez1, Elena Gómez-Marín1

  • 1Genome Biology Department, Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Consejo Superior de Investigaciones Científicas-Universidad de Sevilla-Universidad Pablo de Olavide (CSIC-USE-UPO), Av. Americo Vespucio, 41092 Seville, Spain.

Cell Reports
|March 1, 2024
PubMed
Summary
This summary is machine-generated.

SWI/SNF complexes maintain chromatin accessibility at enhancers, not promoters. Their activity is crucial for genes with specific promoter features, revealing chromatin

Keywords:
BRG1/SMARCA4BRM/SMARCA2CP: Molecular biologyPBAFalternative TSSalternative splicingantisense transcriptioncBAFchromatin remodelingnucleosome occupancy

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Area of Science:

  • Chromatin biology
  • Gene regulation
  • Molecular mechanisms

Background:

  • SWI/SNF complexes are ATP-dependent machines that remodel chromatin.
  • Understanding their specific roles in gene regulation is essential for deciphering cellular processes.

Purpose of the Study:

  • To characterize features of genes dependent on SWI/SNF complexes.
  • To investigate the role of SWI/SNF activity in chromatin accessibility and nucleosome occupancy at promoters and enhancers.

Main Methods:

  • Utilized BRM014, an inhibitor of SWI/SNF ATPase activity.
  • Analyzed chromatin accessibility, nucleosome occupancy, histone marks, and motif enrichment at promoters and regulatory regions.
  • Employed machine-learning models to identify determinants of SWI/SNF dependency.

Main Results:

  • SWI/SNF activity is vital for maintaining chromatin accessibility and nucleosome occupancy at most enhancers, but not typically at promoters.
  • SWI/SNF dependency is observed in genes with low-to-medium expression and specific promoter characteristics (low accessibility, low active marks, high H3K4me1/H3K4me3 ratio, low phasing, TATA-box enrichment).
  • These genes are often associated with the Brahma-related gene 1/Brahma-associated factor (BAF) complex, SWI/SNF-dependent enhancers, and encode signal transduction, developmental, or cell identity factors.

Conclusions:

  • The chromatin landscape of promoters and surrounding regulatory regions dictates SWI/SNF dependency.
  • SWI/SNF complexes play distinct roles in regulating enhancers versus promoters.
  • Specific gene types, particularly non-housekeeping genes, rely on SWI/SNF activity for proper expression through defined chromatin features.