Transcription of a 5' extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoter

Elife. 2017 Sep 14;6:e27420. doi: 10.7554/eLife.27420.

Abstract

Cell differentiation programs require dynamic regulation of gene expression. During meiotic prophase in Saccharomyces cerevisiae, expression of the kinetochore complex subunit Ndc80 is downregulated by a 5' extended long undecoded NDC80 transcript isoform. Here we demonstrate a transcriptional interference mechanism that is responsible for inhibiting expression of the coding NDC80 mRNA isoform. Transcription from a distal NDC80 promoter directs Set1-dependent histone H3K4 dimethylation and Set2-dependent H3K36 trimethylation to establish a repressive chromatin state in the downstream canonical NDC80 promoter. As a consequence, NDC80 expression is repressed during meiotic prophase. The transcriptional mechanism described here is rapidly reversible, adaptable to fine-tune gene expression, and relies on Set2 and the Set3 histone deacetylase complex. Thus, expression of a 5' extended mRNA isoform causes transcriptional interference at the downstream promoter. We demonstrate that this is an effective mechanism to promote dynamic changes in gene expression during cell differentiation.

Keywords: S. cerevisiae; chromatin; chromosomes; genes; interference; mRNA isoform; meiosis; promoter; transcription.

MeSH terms

  • Chromatin / metabolism*
  • Gene Expression Regulation, Fungal*
  • Kinetochores / metabolism
  • Meiosis*
  • Nuclear Proteins / biosynthesis*
  • Promoter Regions, Genetic
  • RNA Isoforms / biosynthesis*
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / biosynthesis*
  • Transcription, Genetic*

Substances

  • Chromatin
  • NDC80 protein, S cerevisiae
  • Nuclear Proteins
  • RNA Isoforms
  • Saccharomyces cerevisiae Proteins