The Loz1 transcription factor from Schizosaccharomyces pombe binds to Loz1 response elements and represses gene expression when zinc is in excess. Issue 6 (24th September 2019)

• Record Type: Journal Article
• Authors: Wilson, Stevin; Liu, Yi‐Hsuan; Cardona‐Soto, Carlos; Wadhwa, Vibhuti; Foster, Mark P.; Bird, Amanda J.
• Is Part Of: Molecular microbiology. Volume 112:Issue 6(2019)
• Page Start: 1701
• Page End: 1717
• Publication Date: 2019-09-24
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14384
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: 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 5ʹ‐CGN(A/C)GATCNTY‐3ʹ, 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. Abstract : In fission yeast the transcription factor Loz1 plays a central role in zinc homeostasis by inhibiting gene expression when zinc is in excess. Here we show that Loz1 DNA binding activity is dependent upon cellular zinc status and that Loz1 binds in a site‐specific manner to Loz1 response elements (LREs) that are located in target genes promoters. These studies provide new mechanistic insight into Loz1 function, and highlight new pathways that are regulated by zinc.