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The DNA repair associated protein Gadd45g regulates the temporal coding of immediate early gene expression and is required for the consolidation of associative fear memory

By Xiang Li, Paul R. Marshall, Laura J. Leighton, Esmi L Zajaczkowski, Timothy W Bredy, Wei Wei

Posted 14 Feb 2018
bioRxiv DOI: 10.1101/265355

We have identified a member of the Growth arrest and DNA damage (Gadd45) family, Gadd45g, which is known to be involved in the regulation of DNA repair, as a key player in the formation of associative fear memory. Gadd45g regulates the temporal dynamics of learning-induced immediate early gene (IEG) expression in the prelimbic prefrontal cortex through its interaction with DNA double-strand break (DSB)-mediated changes in DNA methylation. Our findings suggest a two-hit model of experience-dependent IEG activity and learning that comprises 1) a first wave of IEG expression governed by DSBs followed by an increase in DNA methylation, and 2) a second wave of IEG expression associated with Gadd45g and active DNA demethylation at the same site, which is necessary for memory consolidation.

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