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Epigenetic Variability Confounds Transcriptome but Not Proteome Profiling for Coexpression-based Gene Function

Piotr Grabowski1, Georg Kustatscher2, Juri Rappsilber3,2

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Summary
This summary is machine-generated.

Most gene mRNA coexpression is non-functional and doesn't affect protein levels, especially in housekeeping genes. Epigenetic similarity, not just gene location, drives this, impacting gene function predictions.

Keywords:
Chromatin function or biologyComputational BiologyEpigeneticsGene ExpressionSystems biologygene expression variabilitygene function predictiongenome organisationproteomicstranscriptomics

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Area of Science:

  • Genomics and Molecular Biology
  • Gene Expression Regulation
  • Proteomics

Background:

  • Genes are frequently coexpressed with genomic neighbors, irrespective of functional relation.
  • Small expression changes in mRNA do not always translate to protein level changes.
  • The buffering of protein levels against large, regulated mRNA coexpression changes remains unclear.

Purpose of the Study:

  • To investigate if protein levels are buffered against non-functional mRNA coexpression during large gene expression changes.
  • To analyze mRNA and protein expression in housekeeping genes across diverse mouse tissues.
  • To identify drivers of non-functional mRNA coexpression and their implications for gene function prediction.

Main Methods:

  • Analysis of mRNA and protein expression data for housekeeping genes.
  • Comparison of coexpression patterns across 20 distinct mouse tissues.
  • Assessment of chromosomal proximity and epigenetic similarity as factors influencing coexpression.

Main Results:

  • A significant portion of mRNA coexpression among housekeeping genes is non-functional at the protein level.
  • Chromosomal proximity explains some, but not all, non-functional mRNA coexpression.
  • Epigenetic similarity is identified as the primary driver of non-functional mRNA coexpression across tissues.

Conclusions:

  • Protein coexpression monitoring is superior to mRNA coexpression for gene function prediction.
  • Epigenetic similarity and chromosomal proximity explain non-functional mRNA coexpression.
  • Housekeeping genes may retain broad expression patterns through evolutionary translocation within genomic subcompartments.