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Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
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RNF40 regulates gene expression in an epigenetic context-dependent manner.

Wanhua Xie1, Sankari Nagarajan1, Simon J Baumgart1

  • 1Department of General, Visceral and Pediatric Surgery, Göttingen Center for Molecular Biosciences, University Medical Center Göttingen, Justus-von-Liebig-Weg 11, 37077, Göttingen, Germany.

Genome Biology
|February 18, 2017
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Summary

Histone modification H2Bub1 has context-dependent effects on gene expression, influencing transcription through interactions with other epigenetic regulators like H3K4me3 and H3K27me3.

Keywords:
Broad H3K4me3EnhancerEpigeneticsEzh2FOXL2H2Bub1RNF40

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Area of Science:

  • Epigenetics
  • Gene Regulation
  • Molecular Biology

Background:

  • Monoubiquitination of H2B (H2Bub1) is linked to transcriptional elongation.
  • It was assumed H2Bub1 exclusively positively impacts gene expression.
  • RNF20/RNF40 depletion affects only a subset of genes.

Purpose of the Study:

  • Investigate the context-dependent role of H2Bub1 in gene regulation.
  • Clarify the relationship between H2Bub1 levels and gene expression changes upon RNF40 deletion.
  • Elucidate the interplay between H2Bub1, H3K4me3, and H3K27me3 in gene transcription.

Main Methods:

  • Conditional Rnf40 knockout mouse embryo fibroblasts.
  • Analysis of H2Bub1 occupancy and gene expression.
  • Chromatin immunoprecipitation to assess H3K4me3 and H3K27me3 levels.
  • Gene expression analysis of RNF40-dependent genes and epigenetic modifiers.

Main Results:

  • Genes with low/moderate H2Bub1 are regulated by Rnf40 deletion; high H2Bub1 genes are unaffected.
  • RNF40 deletion leads to H3K4me3 peak narrowing and decreased transcriptional elongation.
  • Upregulated genes (e.g., Foxl2) show enrichment for H3K27me3, decreasing with Rnf40 loss via Ezh2.
  • Enhanced Foxl2 expression correlates with enhancer activation.

Conclusions:

  • H2Bub1 exhibits context-dependent, divergent effects on gene transcription.
  • Epigenetic regulatory protein activity and histone modifications dictate these effects.
  • Findings reveal complexity in histone modification roles in gene regulation.