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

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dc.contributor.authorLal, Snehaen_US
dc.contributor.authorComer, Jonathan M.en_US
dc.contributor.authorKonduri, Purna C.en_US
dc.contributor.authorShah, Ajiten_US
dc.contributor.authorWang, Tianyuanen_US
dc.contributor.authorLewis, Anthonyen_US
dc.contributor.authorShoffner, Granten_US
dc.contributor.authorGuo, Fengen_US
dc.contributor.authorZhang, Lien_US
dc.contributor.utdAuthorLal, Snehaen_US
dc.contributor.utdAuthorComer, Jonathan M.en_US
dc.contributor.utdAuthorKonduri, Purna C.en_US
dc.contributor.utdAuthorWang, Tianyuanen_US
dc.contributor.utdAuthorLewis, Anthonyen_US
dc.contributor.utdAuthorZhang, Lien_US
dc.date.accessioned2018-10-22T19:31:27Z
dc.date.available2018-10-22T19:31:27Z
dc.date.created2017-11-06en_US
dc.date.issued2018-10-22
dc.description.abstractThe 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.en_US
dc.description.departmentSchool of Natural Sciences and Mathematicsen_US
dc.description.sponsorshipNational Institute of General Medical Sciences [R15GM107717]. Funding for open access charge: National Institute of General Medical Sciences [R15GM107717].en_US
dc.identifier.bibliographicCitationLal, 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/gkx1051en_US
dc.identifier.issn1362-4962en_US
dc.identifier.issue1en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/6214
dc.identifier.volume46en_US
dc.language.isoenen_US
dc.publisherOxford University Pressen_US
dc.relation.urihttp://dx.doi.org/10.1093/nar/gkx1051
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2017 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceNucleic Acids Research
dc.subjectGIS1 protein, S cerevisiaeen_US
dc.subjectHistone Demethylasesen_US
dc.subjectJumonji C domainen_US
dc.subjectJumonji Domain-Containing Histone Demethylasesen_US
dc.titleHeme Promotes Transcriptional and Demethylase Activities of Gis1, a Member of the Histone Demethylase JMJD2/KDM4 Familyen_US
dc.type.genrearticleen_US

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