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Carlos Alberto Peralta-Alvarez1,2, Hober Nelson Núñez-Martínez1, Ángel Josué Cerecedo-Castillo1

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Bidirectional gene promoters regulate gene expression beyond local effects. This study shows a specific bidirectional promoter influences distal gene BBX expression via promoter-promoter interactions.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Epigenetics

Background:

  • Human gene promoters exhibit complex regulatory roles beyond local transcription.
  • Bidirectional promoters are common in mammalian genomes, regulating gene pairs.
  • The full functional scope of bidirectional promoters remains largely uninvestigated.

Purpose of the Study:

  • To investigate the long-range gene expression regulatory function of a long non-coding RNA gene promoter.
  • To explore the role of promoter-promoter interactions in gene regulation.

Main Methods:

  • Chromosome conformation capture (3C) techniques were employed.
  • Analysis focused on a specific bidirectional promoter and its interaction with the distal gene BBX promoter.
  • Gene expression levels and promoter-enhancer interactions were assessed after genomic context manipulation.

Main Results:

  • A bidirectional promoter was found to regulate distal gene expression in a target-specific manner through promoter-promoter interactions.
  • Interactions between the bidirectional promoter and the BBX promoter were validated as modulators of BBX transcription.
  • Removal of the bidirectional promoter altered BBX promoter-enhancer interactions, leading to increased gene expression.
  • This long-range regulation was independent of the associated non-coding gene's expression levels.

Conclusions:

  • Bidirectional promoters can exert long-range regulatory control over gene expression.
  • Promoter-promoter interactions mediated by bidirectional promoters are a key mechanism for distal gene regulation.
  • The functional consequences of bidirectional promoters extend beyond their immediate genomic vicinity.