The Loz1 transcription factor from Schizosaccharomyces pombe binds to Loz1 response elements and represses gene expression when zinc is in excess

Mol Microbiol. 2019 Dec;112(6):1701-1717. doi: 10.1111/mmi.14384. Epub 2019 Sep 24.

Abstract

In Schizosaccharomyces pombe, the expression of the zrt1 zinc uptake gene is tightly regulated by zinc status. When intracellular zinc levels are low, zrt1 is highly expressed. However, when zinc levels are high, transcription of zrt1 is blocked in a manner that is dependent upon the transcription factor Loz1. To gain additional insight into the mechanism by which Loz1 inhibits gene expression in high zinc, we used RNA-seq to identify Loz1-regulated genes, and ChIP-seq to analyze the recruitment of Loz1 to target gene promoters. We find that Loz1 is recruited to the promoters of 27 genes that are also repressed in high zinc in a Loz1-dependent manner. We also find that the recruitment of Loz1 to the majority of target gene promoters is dependent upon zinc and the motif 5'-CGN(A/C)GATCNTY-3', which we have named the Loz1 response element (LRE). Using reporter assays, we show that LREs are both required and sufficient for Loz1-mediated gene repression, and that the level of gene repression is dependent upon the number and sequence of LREs. Our results elucidate the Loz1 regulon in fission yeast and provide new insight into how eukaryotic cells are able to respond to changes in zinc availability in the environment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Gene Expression / genetics
  • Gene Expression Regulation, Fungal / genetics
  • Homeostasis
  • Promoter Regions, Genetic / genetics
  • Response Elements / genetics
  • Response Elements / physiology*
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Zinc / metabolism*
  • Zinc Fingers / genetics

Substances

  • Cation Transport Proteins
  • Loz1 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Transcription Factors
  • Zinc