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The JmjC Domain‐containing Regulator Gis1 Is Regulated by Heme and Oxygen
Author(s) -
Cao Thai,
Shah Ajit,
Lal Sneha,
Zhang Li
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.550.20
Subject(s) - demethylase , biochemistry , pas domain , heme , biology , microbiology and biotechnology , chemistry , histone , transcription factor , gene , enzyme
JmjC domain‐containing proteins have demethylase activity and can remove specific methyl groups on histones or other proteins. There are over 100 proteins in diverse organisms known to contain the JmjC domain. These proteins act by oxidizing the methyl group to yield formaldehyde and the unmodified lysine or arginine. Due to the requirement for oxygen for demethylase activity, these proteins can serve as oxygen sensors. The yeast Gis1 is a unique transcriptional regulator belonging to the JHDM3/JMJD2 subfamily of demethylases. Further, Gis1 is highly homologous to the mammalian JmjC domain‐containing JMJD2B protein that is likely to play important roles in histone demethylation, oxygen regulation and hormonal signaling. Recently, our studies showed that Gis1 activity is regulated by both heme and oxygen. Analysis of PDS‐LEU2‐lacZ reporter gene showed a significant increase in PDS reporter gene under high heme concentration. However, a decrease in the Gis1 activity was observed under hypoxia as compared to normoxia. Confocal fluorescent live cell imaging of Gis1 showed that over 95% of the Gis1 protein were nuclear in normoxic cells, while over 90% of Gis1 protein were retained in the cytosol in hypoxic cells. Time course characterization of relocalization of Gis1 showed that Gis1 relocalized in a significantly shorter time period in response to both hypoxia and reoxygenation. Grants: Cecil H. and Ida Green Funds