Heme Promotes Transcriptional and Demethylase Activities of Gis1, a Member of the Histone Demethylase JMJD2/KDM4 Family

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Heme Promotes Transcriptional and Demethylase Activities of Gis1, a Member of the Histone Demethylase JMJD2/KDM4 Family

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Title: Heme Promotes Transcriptional and Demethylase Activities of Gis1, a Member of the Histone Demethylase JMJD2/KDM4 Family
Author(s):
Lal, Sneha;
Comer, Jonathan M.;
Konduri, Purna C.;
Shah, Ajit;
Wang, Tianyuan;
Lewis, Anthony;
Shoffner, Grant;
Guo, Feng;
Zhang, Li
Date Created: 2017-11-06
Item Type: article
Keywords: GIS1 protein, S cerevisiae
Histone Demethylases
Jumonji C domain
Jumonji Domain-Containing Histone Demethylases
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.
Publisher: Oxford University Press
ISSN: 1362-4962
Source: Nucleic Acids Research
Link to Related Resource: http://dx.doi.org/10.1093/nar/gkx1051
Persistent Link: http://hdl.handle.net/10735.1/6214
Bibliographic Citation: Lal, Sneha, Jonathan M. Comer, Purna C. Konduri, Ajit Shah, et al. 2018. "Heme promotes transcriptional and demethylase activities of Gis1, a member of the histone demethylase JMJD2/KDM4 family" Nucleic Acids Research 46(1), doi:10.1093/nar/gkx1051
Terms of Use: CC BY 4.0 (Attribution)
©2017 The Authors
Sponsors: National Institute of General Medical Sciences [R15GM107717]. Funding for open access charge: National Institute of General Medical Sciences [R15GM107717].

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CC BY 4.0 (Attribution) Except where otherwise noted, this item's license is described as CC BY 4.0 (Attribution)