Mood stabilizers lithium and valproates are widely used in the treatment of bipolar disorder. It has been shown that these drugs can affect the inositol monophosphatase activity and thus the inositol de novo biosynthesis. However, the molecular mechanism of this action has thus far been vague. As such, characterizing the regulation of the gene encoding inositol monophosphatase at the molecular level can help to understand the bipolar disorder. As the model organism, the inositol monophosphatase is encoded by INM1 in Saccharomyces cerevisiae. In this study, we showed, using real-time reverse transcriptase polymerase chain reaction analysis, that INM1 is expressed in the presence of inositol, suggesting that the presence of inositol is required for INM1 transcriptional activation. We also demonstrated, using chromatin immunoprecipitation, that Ino2p is present at the promoter under uninduced conditions. Upon induction, Ino2p dissociates from the INM1 promoter. Furthermore, chromatin remodelers Ino80p and Snf2p are recruited to INM1 promoter upon induction as well as histone acetylases Gcn5p and Esa1p. Altogether, we have provided the evidence which describes how the transcriptional activator and coactivators participate in INM1 activation.

• PMID: 25211324
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Zhang L, Di J

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