NGF/PI3K signaling-mediated epigenetic regulation of delta opioid receptor gene expression |
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| Authors: | Chen Yulong L Law Ping-Yee Loh Horace H |
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| Affiliation: | a Department of Biological Sciences, Binghamton University, The State University of New York, 4400 Vestal Parkway E, Binghamton, NY 13902, USA
b Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA |
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| Abstract: | The G protein-coupled delta opioid receptor gene (dor) has been associated with neuronal survival, differentiation, and neuroprotection. Our previous study identified PI3K/Akt/NF-κB signaling is a main downstream signaling pathway in nerve growth factor (NGF)-induced temporal expression of the dor gene in the PC12 cell model. It is still unknown how NGF/PI3K signaling regulates the expression of the dor gene in the nucleus. In the current study, we investigated how PI3K signaling affected epigenetic modifications of histone H3 Lys9 (H3K9) in the 5′-UTR region of the rat dor gene locus. NGF treatment resulted in the global reversal of H3K9 trimethylation in cells. Moreover, the locus-specific reversal of H3K9 trimethylation and acetylation of H3K9 were dependent upon NGF/PI3K signaling and temporally well correlated with NGF-induced gene expression. These results indicate the importance of epigenetic modifications of H3K9, particularly the reversal of trimethylated H3K9, in the regulation of NGF/PI3K-dependent genes during neuronal differentiation. |
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| Keywords: | Akt Chromatin remodeling Delta opioid receptor Histone modification Lysine trimethylation NF-κB NGF PI3K |
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