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Related Experiment Video

Updated: Jul 12, 2025

Generation of Native Chromatin Immunoprecipitation Sequencing Libraries for Nucleosome Density Analysis
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SEM: sized-based expectation maximization for characterizing nucleosome positions and subtypes.

Jianyu Yang1, Kuangyu Yen2,3, Shaun Mahony1

  • 1Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA.

Biorxiv : the Preprint Server for Biology
|October 31, 2023
PubMed
Summary
This summary is machine-generated.

A new tool, Size-based Expectation Maximization (SEM), identifies diverse nucleosome types from MNase-seq data. SEM reveals short-fragment nucleosomes in regulatory regions, aiding the study of atypical nucleosomes and their functions.

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Area of Science:

  • * Molecular Biology
  • * Genomics
  • * Epigenetics

Background:

  • * Nucleosome profiling commonly uses MNase-seq, assuming uniform 147bp DNA protection.
  • * Existing analysis tools overlook shorter DNA fragments, potentially missing regulatory roles of atypical nucleosomes.
  • * Variation in nucleosome DNA protection length is linked to histone composition and chemical modifications.

Approach:

  • * Introduced Size-based Expectation Maximization (SEM), a novel package for nucleosome analysis.
  • * SEM utilizes a hierarchical Gaussian mixture model to identify nucleosome positions and subtypes.
  • * Nucleosome subtypes are automatically classified based on protected DNA fragment length distributions.

Key Points:

  • * SEM achieves comparable accuracy to existing packages while uniquely identifying nucleosome subtypes.
  • * Analysis of mouse embryonic stem cell data revealed three nucleosome types: short-fragment, canonical, and di-nucleosomes.
  • * Short-fragment nucleosomes in accessible regions, termed 'fragile nucleosomes', associate with regulatory elements and chromatin remodelers.

Conclusions:

  • * SEM effectively distinguishes diverse nucleosome subtypes from MNase-seq data.
  • * This capability enables deeper investigation into the functional roles of non-standard nucleosomes.
  • * The findings highlight the importance of considering nucleosome heterogeneity in genomic studies.