AU-rich element-binding protein negatively regulates CCAAT enhancer-binding protein mRNA stability during long-term synaptic plasticity in Aplysia

The consolidation of long-term memory for sensitization and synaptic facilitation in Aplysia requires synthesis of new mRNA including the immediate early gene Aplysia CCAAT enhancer-binding protein (ApC/EBP). After the rapid induction of ApC/EBP expression in response to repeated treatments of 5-hydroxytryptamine (5-HT), ApC/EBP mRNA is temporarily expressed in sensory neurons of sensory-to-motor synapses. However, the molecular mechanism underlying the rapid degradation of ApC/EBP transcript is not known. Here, we cloned an AU-rich element (ARE)-binding protein, ApAUF1, which functions as a destabilizing factor for ApC/EBP mRNA. ApAUF1 was found to bind to the 3′ UTR of ApC/EBP mRNA that contains AREs and subsequently reduces the expression of ApC/EBP 3′ UTR-containing reporter genes. Moreover, overexpression of ApAUF1 inhibited the induction of ApC/EBP mRNA in sensory neurons and also impaired long-term facilitation of sensory-to-motor synapses by repetitive 5-HT treatments. These results provide evidence for a critical role of the posttranscriptional modification of ApC/EBP mRNA during the consolidation of synaptic plasticity.

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Inhibition of Histone Deacetylase Reinstates Hippocampus-Dependent Long-Term Synaptic Plasticity and Associative Memory in Sleep-Deprived Mice

Cerebral Cortex ◽

10.1093/cercor/bhaa041 ◽

2020 ◽

Vol 30 (7) ◽

pp. 4169-4182 ◽

Cited By ~ 1

Author(s):

Lik-Wei Wong ◽

Yee Song Chong ◽

Win Lee Edwin Wong ◽

Sreedharan Sajikumar

Keyword(s):

Synaptic Plasticity ◽

Histone Deacetylase ◽

Associative Memory ◽

Binding Protein ◽

Memory Function ◽

Critical Role ◽

Long Term Memory ◽

Epigenetic Mechanisms ◽

Creb Binding Protein

Abstract Sleep plays an important role in the establishment of long-term memory; as such, lack of sleep severely impacts domains of our health including cognitive function. Epigenetic mechanisms regulate gene transcription and protein synthesis, playing a critical role in the modulation of long-term synaptic plasticity and memory. Recent evidences indicate that transcriptional dysregulation as a result of sleep deprivation (SD) may contribute to deficits in plasticity and memory function. The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA), also known as Vorinostat, a clinically approved drug for human use, has been shown to ameliorate cognitive deficits in several neurological disease models. To further explore the therapeutic effect of SAHA, we have examined its potential role in improving the SD-mediated impairments in long-term plasticity, associative plasticity, and associative memory. Here we show that SAHA preserves long-term plasticity, associative plasticity, and associative memory in SD hippocampus. Furthermore, we find that SAHA prevents SD-mediated epigenetic changes by upregulating histone acetylation, hence preserving the ERK–cAMP-responsive element-binding protein (CREB)/CREB-binding protein–brain-derived neurotrophic factor pathway in the hippocampus. These data demonstrate that modifying epigenetic mechanisms via SAHA can prevent or reverse impairments in long-term plasticity and memory that result from sleep loss. Thus, SAHA could be a potential therapeutic agent in improving SD-related memory deficits.

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Fornix-Dependent Induction of Hippocampal CCAAT Enhancer-Binding Protein β and δ Co-Localizes with Phosphorylated cAMP Response Element-Binding Protein and Accompanies Long-Term Memory Consolidation

Journal of Neuroscience ◽

10.1523/jneurosci.21-01-00084.2001 ◽

2001 ◽

Vol 21 (1) ◽

pp. 84-91 ◽

Cited By ~ 119

Author(s):

Stephen M. Taubenfeld ◽

Kjesten A. Wiig ◽

Barbara Monti ◽

Bridget Dolan ◽

Gabriella Pollonini ◽

...

Keyword(s):

Memory Consolidation ◽

Binding Protein ◽

Camp Response Element Binding ◽

Long Term Memory ◽

Camp Response Element ◽

Response Element ◽

Term Memory ◽

Enhancer Binding Protein ◽

Element Binding Protein

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The Herpesvirus Saimiri Replication and Transcription Activator Acts Synergistically with CCAAT Enhancer Binding Protein Alpha To Activate the DNA Polymerase Promoter

Journal of Virology ◽

10.1128/jvi.79.21.13548-13560.2005 ◽

2005 ◽

Vol 79 (21) ◽

pp. 13548-13560 ◽

Cited By ~ 1

Author(s):

Louise Wakenshaw ◽

Matthew S. Walters ◽

Adrian Whitehouse

Keyword(s):

Dna Polymerase ◽

Binding Protein ◽

Lytic Replication ◽

Early Gene ◽

Herpesvirus Saimiri ◽

Sequence Motif ◽

Gene Promoters ◽

Transcription Activator ◽

Enhancer Binding Protein ◽

Ccaat Enhancer Binding Protein

ABSTRACT The open reading frame (ORF) 50 gene product, also known as the replication and transcription activator (Rta), is an immediate-early gene which is well conserved among all gamma-2 herpesviruses and plays a pivotal role in regulating the latent-lytic switch. Herpesvirus saimiri (HVS) ORF 50a functions as a sequence-specific transactivator capable of activating delayed-early (DE) gene expression via binding directly to an ORF 50 response element (RE) within the respective promoter. Analysis of the ORF 50 REs have identified two distinct types within HVS gene promoters. The first comprises a consensus sequence motif, CCN9GG, the second an AT-rich sequence. Here we demonstrate that ORF 50a is capable of transactivating the DE ORF 9 promoter which encodes the DNA polymerase. Deletion analysis of the ORF 9 promoter mapped the ORF 50 RE to a 95-bp region situated 126 bp upstream of the initiation codon. Gel retardation analysis further mapped the RE to a 28-bp fragment, which was able to confer ORF 50 responsiveness on an enhancerless simian virus 40 minimal promoter. Furthermore, sequence analysis identified multiple CCAAT enhancer binding protein alpha (C/EBPα) binding sites within the ORF 9 promoter and specifically two within the close vicinity of the AT-rich ORF 50 RE. Analysis demonstrated that the HVS ORF 50a and C/EBPα proteins associate with the ORF 9 promoter in vivo, interact directly, and synergistically activate the ORF 9 promoter by binding to adjacent binding motifs. Overall, these data suggest a cooperative interaction between HVS ORF 50a and C/EBPα proteins to activate the DNA polymerase promoter during early stages of the lytic replication cycle.

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