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Histone modifications influence skipped exons inclusion.

Yue Hou1, Huan Huang1, Wenqiao Hu1

  • 11 State Key Laboratory of Bioelectronics, School of Biology Science and Medical Engineering, Southeast University, Nanjing, P. R. China.

Journal of Bioinformatics and Computational Biology
|February 10, 2017
PubMed
Summary

Histone modifications influence alternative splicing (AS). Active histone marks in skipped exons (SEs) negatively correlate with their inclusion, suggesting a regulatory role in gene expression complexity.

Keywords:
Histone modificationalternative splicingskipped exon

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Area of Science:

  • Molecular Biology
  • Genetics
  • Epigenetics

Background:

  • Alternative splicing (AS) generates diverse mRNA transcripts from single genes, impacting genomic complexity, disease, and development.
  • Histone modifications are crucial regulators of both transcription initiation and mRNA splicing processes.

Purpose of the Study:

  • To investigate the relationship between alternative splicing and histone modifications in flanking regions.
  • To analyze publicly available data from human cell lines (GM12878 and K562) to understand this link.

Main Methods:

  • Classification of exons based on inclusion levels: included skipped exons, excluded skipped exons, and expressed constitutive exons.
  • Analysis of publicly available genomic data from GM12878 and K562 cell lines.
  • Correlation analysis between exon inclusion levels and histone modification enrichment.

Main Results:

  • A negative correlation was observed between skipped exon (SE) inclusion levels and the enrichment of active histone marks within SEs.
  • Active histone modifications were found to be enriched in upstream exons of SEs, particularly near the 5' splice sites.
  • Nucleosome occupancy showed minimal impact on SE inclusion levels.

Conclusions:

  • Histone modifications play a significant role in regulating alternative splicing.
  • Enrichment of active histone marks near 5' splice sites in upstream exons may facilitate the recruitment of RNA Polymerase II and associated proteins, promoting AS.
  • An integrated model was proposed to elucidate the mechanism by which histone modifications influence pre-mRNA splicing.