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Evaluating Chromatin Accessibility Differences Across Multiple Primate Species Using a Joint Modeling Approach.

Lee E Edsall1,2,3, Alejandro Berrio4, William H Majoros5

  • 1Center for Genomic and Computational Biology, Duke University.

Genome Biology and Evolution
|October 11, 2019
PubMed
Summary
This summary is machine-generated.

We developed a new method to analyze chromatin accessibility changes across species, revealing distinct patterns in regulatory element evolution and conservation. This advance helps understand how gene expression evolves.

Keywords:
cis-regulatory evolutionchromatin accessibilitycomparative functional genomicspositive selectiontranscriptional regulation

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Area of Science:

  • Evolutionary biology
  • Genomics
  • Molecular biology

Background:

  • Changes in transcriptional regulation drive phenotypic evolution.
  • The role of chromatin accessibility evolution in gene expression is largely unknown.

Purpose of the Study:

  • To develop a novel method for identifying differential chromatin accessibility between species.
  • To investigate the evolutionary patterns of regulatory elements using this new approach.

Main Methods:

  • Developed a joint modeling approach to identify differential DNase I Hypersensitive (DHS) sites across multiple species.
  • Applied the method to fibroblast cells from five primate species (human, chimpanzee, gorilla, orangutan, rhesus macaque).

Main Results:

  • Identified 89,744 DHS sites, with 41% showing differential accessibility using the joint model versus 33% with pairwise comparisons.
  • Nondifferential DHS sites are enriched for nucleotide conservation.
  • Differential DHS sites near transcription start sites (TSS) exhibit distinct characteristics compared to distal sites.

Conclusions:

  • The joint modeling approach offers a sensitive and principled way to detect evolutionary changes in chromatin accessibility.
  • Distinct classes of regulatory elements show varying patterns of selection, genomic location, and cell type specificity.
  • This work provides insights into the mechanisms of gene expression evolution driven by chromatin changes.