scholarly journals The DNA repair associated protein Gadd45γ regulates the temporal coding of immediate early gene expression and is required for the consolidation of associative fear memory

2018 ◽  
Author(s):  
Xiang Li ◽  
Paul R. Marshall ◽  
Laura J. Leighton ◽  
Esmi L. Zajaczkowski ◽  
Timothy W. Bredy ◽  
...  

AbstractVisual abstractWe have identified a member of the Growth arrest and DNA damage (Gadd45) family, Gadd45γ, which is known to be involved in the regulation of DNA repair, as a key player in the formation of associative fear memory. Gadd45γ 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 Gadd45γ and active DNA demethylation at the same site, which is necessary for memory consolidation.Significance statementHow does the pattern of immediate early gene (IEG) transcription in the brain relate to the storage and accession of information, and what controls these patterns? This paper explores how GADD45γ, a gene that is known to be involved with DNA modification and repair, regulates the temporal coding of IEGs underlying associative learning and memory. We reveal that, during fear learning, GADD45γ serves to act as a coordinator of IEG expression and subsequent memory consolidation by directing temporally specific changes in active DNA demethylation at the promoter of plasticity-related IEGs.

2009 ◽  
Vol 2 (1) ◽  
pp. 7 ◽  
Author(s):  
Naoko Inoue ◽  
Harumi Nakao ◽  
Rika Migishima ◽  
Toshiaki Hino ◽  
Minoru Matsui ◽  
...  

2015 ◽  
Vol 35 (2) ◽  
pp. 819-830 ◽  
Author(s):  
Daisuke Nakayama ◽  
Hirokazu Iwata ◽  
Chie Teshirogi ◽  
Yuji Ikegaya ◽  
Norio Matsuki ◽  
...  

2020 ◽  
Author(s):  
Anumita Samanta ◽  
Laurens S van Rongen ◽  
Janine I. Rossato ◽  
Justin Jacobse ◽  
Robby Schoenfeld ◽  
...  

AbstractSleep is important for memory consolidation, especially the process of systems consolidation should occur during sleep. While a significant amount of research has been done in regards to the effect of sleep on behavior and certain mechanisms during sleep, until now evidence is lacking that sleep leads to consolidation across the system. Here, we investigated the role of sleep in consolidation of spatial memory in the watermaze in both rats and humans using allocentric and egocentric based training. Combining behavior with immediate early gene expression analysis in rodents and functional MR imaging in humans, elucidated similar behavioral and neural effects in both species. Rats and humans showed a benefit of sleep on behavior. Interestingly, sleep led to systems-wide retrieval network in both species in both training conditions. Thus, we provide cross-species evidence for memory consolidation on the system-level occurring during sleep.Significance StatementProcesses occurring during sleep such as memory reactivations are proposed to lead to consolidation from the initial hippocampal memory representation to long-lasting cortical representations, this is known as systems consolidation. By combining behavioral measurements in the watermaze with immediate early gene expression analysis in rats and function magnetic resonance imaging in humans, we could show a benefit of sleep on behavioral memory performance. And, sleep lead to systems-wide changes in the retrieval network. These results are the first direct evidence supporting the role of sleep for systems-wide memory consolidation in both rats and humans.


2019 ◽  
Author(s):  
Stéfanie Graindorge ◽  
Valérie Cognat ◽  
Philippe Johann to Berens ◽  
Jérôme Mutterer ◽  
Jean Molinier

AbstractPlants are exposed to the damaging effect of sunlight that induces DNA photolesions. In order to maintain genome integrity, specific DNA repair pathways are mobilized. Upon removal of UV-induced DNA lesions, the accurate re-establishment of epigenome landscape is expected to be a prominent step of these DNA repair pathways. However, it remains poorly documented whether DNA methylation is accurately maintained at photodamaged sites and how photodamage repair pathways contribute to the maintenance of genome/methylome integrities. Using genome wide approaches, we report that UV-C irradiation leads to asymmetric DNA methylation changes. We identified that the specific DNA repair pathways involved in the repair of UV-induced DNA lesions, Direct Repair (DR) and Global Genome Repair (GGR), prevent the excessive alterations of DNA methylation landscape. Moreover, we identified that UV-C irradiation induced chromocenter reorganization and that photodamage repair factors control this dynamics. The methylome changes rely on misregulation of maintenance, de novo and active DNA demethylation pathways highlighting that molecular processes related to genome and methylome integrities are closely interconnected. Importantly, we identified that photolesions are sources of DNA methylation changes in both, constitutive and facultative heterochromatin. This study unveils that DNA repair factors, together with small RNA, act to accurately maintain both genome and methylome integrities at photodamaged silent genomic regions, strengthening the idea that plants have evolved sophisticated interplays between DNA methylation dynamics and DNA repair.


2012 ◽  
Author(s):  
Christopher B. Sturdy ◽  
Marc T. Avey ◽  
Laurie L. Bloomfield ◽  
Julie E. Elie ◽  
Todd M. Freeberg ◽  
...  

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