ArticleNucleic acids research2018
Heme promotes transcriptional and demethylase activities of Gis1, a member of the histone demethylase JMJD2/KDM4 family.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 17 citations in OpenAlex.
- Mechanism of enhanced salt tolerance in Saccharomyces cerevisiae by CRZ1 overexpression.Scientific reports · 2024Article
- Transcriptional noise adjusted for expression levels reveals genes with high transcriptional noise that are highly expressed, functionally related, and co-regulated in yeast.Current genetics · 2022Article
- Article
- Ready, SET, Go: Post-translational regulation of the histone lysine methylation network in budding yeast.The Journal of biological chemistry · 2021Review
- Article
- The Multifaceted Role of Heme in Cancer.Frontiers in oncology · 2019Review
- Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The yeast Gis1 protein is a transcriptional regulator belonging to the JMJD2/KDM4 subfamily of demethylases that contain a JmjC domain, which are highly conserved from yeast to humans. They have important functions in histone methylation, cellular signaling and tumorigenesis. Besides serving as a cofactor in many proteins, heme is known to directly regulate the activities of proteins ranging from transcriptional regulators to potassium channels. Here, we report a novel mechanism governing heme regulation of Gis1 transcriptional and histone demethylase activities. We found that two Gis1 modules, the JmjN + JmjC domain and the zinc finger (ZnF), can bind to heme specifically in vitro. In vivo functional analysis showed that the ZnF, not the JmjN + JmjC domain, promotes heme activation of transcriptional activity. Likewise, measurements of the demethylase activity of purified Gis1 proteins showed that full-length Gis1 and the JmjN + JmjC domain both possess demethylase activity. However, heme potentiates the demethylase activity of full-length Gis1, but not that of the JmjN + JmjC domain, which can confer heme activation of transcriptional activity in an unrelated protein. These results demonstrate that Gis1 represents a novel class of multi-functional heme sensing and signaling proteins, and that heme binding to the ZnF stimulates Gis1 demethylase and transcriptional activities.
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