The transcriptional activator Ino2p dissociates from the yeast INM1 promoter in induction.

Abstract

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.

• Authors: Lingzhi Zhang, Jing Di
• Journal: DNA and cell biology (DNA Cell Biol) Vol. 33 Issue 12 Pg. 863-8 (Dec 2014) ISSN: 1557-7430 [Electronic] United States
• PMID: 25211324 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• INO2 protein, S cerevisiae
• Saccharomyces cerevisiae Proteins
• Inositol
• Esa1 protein, S cerevisiae
• GCN5 protein, S cerevisiae
• Histone Acetyltransferases
• Phosphoric Monoester Hydrolases
• myo-inositol-1 (or 4)-monophosphatase

Topics

• Basic Helix-Loop-Helix Transcription Factors (metabolism)
• Enzyme Induction
• Gene Expression Regulation, Fungal
• Histone Acetyltransferases (metabolism)
• Inositol (physiology)
• Phosphoric Monoester Hydrolases (genetics)
• Promoter Regions, Genetic
• Protein Binding
• Saccharomyces cerevisiae (enzymology, genetics)
• Saccharomyces cerevisiae Proteins (metabolism)
• Transcriptional Activation