A function of TPL/TBL1-type corepressors is to nucleate the assembly of the preinitiation complex

J Cell Biol. 2025 Feb 3;224(2):e202404103. doi: 10.1083/jcb.202404103. Epub 2024 Dec 9.

Abstract

The plant corepressor TPL is recruited to diverse chromatin contexts, yet its mechanism of repression remains unclear. Previously, we leveraged the fact that TPL retains its function in a synthetic transcriptional circuit in the yeast model Saccharomyces cerevisiae to localize repressive function to two distinct domains. Here, we employed two unbiased whole-genome approaches to map the physical and genetic interactions of TPL at a repressed locus. We identified SPT4, SPT5, and SPT6 as necessary for repression with SPT4 acting as a bridge connecting TPL to SPT5 and SPT6. We discovered the association of multiple additional constituents of the transcriptional preinitiation complex at TPL-repressed promoters, specifically those involved early in transcription initiation. These findings were validated in yeast and plants, including a novel method to analyze the conditional loss of function of essential genes in plants. Our findings support a model where TPL nucleates preassembly of the transcription activation machinery to facilitate the rapid onset of transcription once repression is relieved.

MeSH terms

  • Arabidopsis Proteins* / genetics
  • Arabidopsis Proteins* / metabolism
  • Arabidopsis* / genetics
  • Arabidopsis* / metabolism
  • Chromosomal Proteins, Non-Histone
  • Co-Repressor Proteins / genetics
  • Co-Repressor Proteins / metabolism
  • Gene Expression Regulation, Plant
  • Histone Chaperones
  • Promoter Regions, Genetic* / genetics
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism
  • Transcription Initiation, Genetic
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • Arabidopsis Proteins
  • topless protein, Arabidopsis
  • Repressor Proteins
  • Transcriptional Elongation Factors
  • SPT5 transcriptional elongation factor
  • SPT6 protein, S cerevisiae
  • Co-Repressor Proteins
  • Chromosomal Proteins, Non-Histone
  • Histone Chaperones