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Decoding regulatory associations of G-quadruplex with epigenetic and transcriptomic functional components.

Shuyi Fang1, Sheng Liu2,3, Danzhou Yang4,5

  • 1Department of BioHealth Informatics, Indiana University School of Informatics and Computing, Indiana University-Purdue University Indianapolis, Indianapolis, IN, United States.

Frontiers in Genetics
|September 12, 2022
PubMed
Summary

G-quadruplex (G4) structures influence gene expression through diverse epigenetic interactions. This study reveals G4s can positively or negatively regulate transcription based on their genomic location and DNA strand, impacting gene regulation.

Keywords:
DNA methylationG-quadruplexG4 feetenhancergene expressionmotifopen chromatintranscription

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Area of Science:

  • Genomics
  • Epigenetics
  • Molecular Biology

Background:

  • G-quadruplex (G4) DNA structures are increasingly recognized for their role in gene regulation.
  • Understanding the interplay between G4s and other epigenetic elements is crucial for deciphering transcriptional control.

Purpose of the Study:

  • To investigate the associations between different confidence levels of G4 sites and various epigenetic regulatory elements in the human genome.
  • To explore how G4 structures, based on their genomic location and DNA strand, correlate with gene expression.
  • To identify transcription factors and sequence motifs associated with G4 formation.

Main Methods:

  • Integrative analysis of in-silicon predicted and ChIP-seq G4 multi-omics data.
  • Classification of G4 sites into high-confidence (G4-II), ChIP-seq detected (G4-I), and predicted motif (G4-III) groups.
  • Elastic net regression modeling to assess G4-gene expression correlations.
  • Motif analysis and GC/TA content assessment in G4 flanking regions.

Main Results:

  • G4 structures exhibit dual roles in gene expression regulation, dependent on their genomic location relative to genes and the DNA strand involved.
  • Specific transcription factors were found to be over-represented in regions with G4 emergence.
  • Distinct consensus sequences and base compositions (high GC vs. high TA) were identified in the flanking regions of different G4 groups.

Conclusions:

  • G4 formations and predictions are comprehensively associated with epigenetic and transcriptional regulatory elements.
  • These associations suggest a coordinated role for G4s in modulating gene transcription.
  • The findings provide insights into the complex mechanisms governing G4-mediated gene expression control.